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Category Archives: Genetic Therapy

Gene therapy – Wikipedia

Medical field

Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect[1] or the treatment of disease by repairing or reconstructing defective genetic material.[2] The first attempt at modifying human DNA was performed in 1980, by Martin Cline, but the first successful nuclear gene transfer in humans, approved by the National Institutes of Health, was performed in May 1989.[3] The first therapeutic use of gene transfer as well as the first direct insertion of human DNA into the nuclear genome was performed by French Anderson in a trial starting in September 1990. It is thought to be able to cure many genetic disorders or treat them over time.

Between 1989 and December 2018, over 2,900 clinical trials were conducted, with more than half of them in phase I.[4] As of 2017, Spark Therapeutics' Luxturna (RPE65 mutation-induced blindness) and Novartis' Kymriah (Chimeric antigen receptor T cell therapy) are the FDA's first approved gene therapies to enter the market. Since that time, drugs such as Novartis' Zolgensma and Alnylam's Patisiran have also received FDA approval, in addition to other companies' gene therapy drugs. Most of these approaches utilize adeno-associated viruses (AAVs) and lentiviruses for performing gene insertions, in vivo and ex vivo, respectively. AAVs are characterized by stabilizing the viral capsid, lower immunogenicity, ability to transduce both dividing and nondividing cells, the potential to integrate site specifically and to achieve long-term expression in the in-vivo treatment. (Gorell et al. 2014) ASO / siRNA approaches such as those conducted by Alnylam and Ionis Pharmaceuticals require non-viral delivery systems, and utilize alternative mechanisms for trafficking to liver cells by way of GalNAc transporters.

The concept of gene therapy is to fix a genetic problem at its source. If, for instance, a mutation in a certain gene causes the production of a dysfunctional protein resulting (usually recessively) in an inherited disease, gene therapy could be used to deliver a copy of this gene that does not contain the deleterious mutation and thereby produces a functional protein. This strategy is referred to as gene replacement therapy and is employed to treat inherited retinal diseases.[5][6]

While the concept of gene replacement therapy is mostly suitable for recessive diseases, novel strategies have been suggested that are capable of also treating conditions with a dominant pattern of inheritance.

Not all medical procedures that introduce alterations to a patient's genetic makeup can be considered gene therapy. Bone marrow transplantation and organ transplants in general have been found to introduce foreign DNA into patients.[13]

Gene therapy was conceptualized in 1972, by authors who urged caution before commencing human gene therapy studies.

The first attempt, an unsuccessful one, at gene therapy (as well as the first case of medical transfer of foreign genes into humans not counting organ transplantation) was performed by Martin Cline on 10 July 1980.[14][15] Cline claimed that one of the genes in his patients was active six months later, though he never published this data or had it verified[16] and even if he is correct, it's unlikely it produced any significant beneficial effects treating beta thalassemia.[medical citation needed]

After extensive research on animals throughout the 1980s and a 1989 bacterial gene tagging trial on humans, the first gene therapy widely accepted as a success was demonstrated in a trial that started on 14 September 1990, when Ashanthi DeSilva was treated for ADA-SCID.[17]

The first somatic treatment that produced a permanent genetic change was initiated in 1993.[18] The goal was to cure malignant brain tumors by using recombinant DNA to transfer a gene making the tumor cells sensitive to a drug that in turn would cause the tumor cells to die.[19]

The polymers are either translated into proteins, interfere with target gene expression, or possibly correct genetic mutations. The most common form uses DNA that encodes a functional, therapeutic gene to replace a mutated gene. The polymer molecule is packaged within a "vector", which carries the molecule inside cells.[medical citation needed]

Early clinical failures led to dismissals of gene therapy. Clinical successes since 2006 regained researchers' attention, although as of 2014[update], it was still largely an experimental technique.[20] These include treatment of retinal diseases Leber's congenital amaurosis[5][21][22][23] and choroideremia,[24] X-linked SCID,[25] ADA-SCID,[26][27] adrenoleukodystrophy,[28] chronic lymphocytic leukemia (CLL),[29] acute lymphocytic leukemia (ALL),[30] multiple myeloma,[31] haemophilia,[27] and Parkinson's disease.[32] Between 2013 and April 2014, US companies invested over $600 million in the field.[33]

The first commercial gene therapy, Gendicine, was approved in China in 2003, for the treatment of certain cancers.[34] In 2011, Neovasculgen was registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease, including critical limb ischemia.[35]In 2012, Glybera, a treatment for a rare inherited disorder, lipoprotein lipase deficiency, became the first treatment to be approved for clinical use in either Europe or the United States after its endorsement by the European Commission.[20][36]

Following early advances in genetic engineering of bacteria, cells, and small animals, scientists started considering how to apply it to medicine. Two main approaches were considered replacing or disrupting defective genes.[37] Scientists focused on diseases caused by single-gene defects, such as cystic fibrosis, haemophilia, muscular dystrophy, thalassemia, and sickle cell anemia. Glybera treats one such disease, caused by a defect in lipoprotein lipase.[36]

DNA must be administered, reach the damaged cells, enter the cell and either express or disrupt a protein.[38] Multiple delivery techniques have been explored. The initial approach incorporated DNA into an engineered virus to deliver the DNA into a chromosome.[39][40] Naked DNA approaches have also been explored, especially in the context of vaccine development.[41]

Generally, efforts focused on administering a gene that causes a needed protein to be expressed. More recently, increased understanding of nuclease function has led to more direct DNA editing, using techniques such as zinc finger nucleases and CRISPR. The vector incorporates genes into chromosomes. The expressed nucleases then knock out and replace genes in the chromosome. As of 2014[update] these approaches involve removing cells from patients, editing a chromosome and returning the transformed cells to patients.[42]

Gene editing is a potential approach to alter the human genome to treat genetic diseases,[7] viral diseases,[43] and cancer.[44][45] As of 2020[update] these approaches are being studied in clinical trials.[46][47]

Gene therapy may be classified into two types:

In somatic cell gene therapy (SCGT), the therapeutic genes are transferred into any cell other than a gamete, germ cell, gametocyte, or undifferentiated stem cell. Any such modifications affect the individual patient only, and are not inherited by offspring. Somatic gene therapy represents mainstream basic and clinical research, in which therapeutic DNA (either integrated in the genome or as an external episome or plasmid) is used to treat disease.[48]

Over 600 clinical trials utilizing SCGT are underway[when?] in the US. Most focus on severe genetic disorders, including immunodeficiencies, haemophilia, thalassaemia, and cystic fibrosis. Such single gene disorders are good candidates for somatic cell therapy. The complete correction of a genetic disorder or the replacement of multiple genes is not yet possible. Only a few of the trials are in the advanced stages.[49][needs update]

In germline gene therapy (GGT), germ cells (sperm or egg cells) are modified by the introduction of functional genes into their genomes. Modifying a germ cell causes all the organism's cells to contain the modified gene. The change is therefore heritable and passed on to later generations. Australia, Canada, Germany, Israel, Switzerland, and the Netherlands[50] prohibit GGT for application in human beings, for technical and ethical reasons, including insufficient knowledge about possible risks to future generations[50] and higher risks versus SCGT.[51] The US has no federal controls specifically addressing human genetic modification (beyond FDA regulations for therapies in general).[50][52][53][54]

The delivery of DNA into cells can be accomplished by multiple methods. The two major classes are recombinant viruses (sometimes called biological nanoparticles or viral vectors) and naked DNA or DNA complexes (non-viral methods).[55]

In order to replicate, viruses introduce their genetic material into the host cell, tricking the host's cellular machinery into using it as blueprints for viral proteins. Retroviruses go a stage further by having their genetic material copied into the genome of the host cell. Scientists exploit this by substituting a virus's genetic material with therapeutic DNA or RNA. A number of viruses have been used for human gene therapy, including retroviruses, adenoviruses, herpes simplex, vaccinia, and adeno-associated virus.[4] Like the genetic material (DNA or RNA) in viruses, therapeutic DNA can be designed to simply serve as a temporary blueprint that is degraded naturally or (at least theoretically) to enter the host's genome, becoming a permanent part of the host's DNA in infected cells.

Non-viral vectors for gene therapy[56] present certain advantages over viral methods, such as large scale production and low host immunogenicity. However, non-viral methods initially produced lower levels of transfection and gene expression, and thus lower therapeutic efficacy. Newer technologies offer promise of solving these problems, with the advent of increased cell-specific targeting and subcellular trafficking control.

Methods for non-viral gene therapy include the injection of naked DNA, electroporation, the gene gun, sonoporation, magnetofection, the use of oligonucleotides, lipoplexes, dendrimers, and inorganic nanoparticles.

More recent approaches, such as those performed by companies such as Ligandal, offer the possibility of creating cell-specific targeting technologies for a variety of gene therapy modalities, including RNA, DNA and gene editing tools such as CRISPR. Other companies, such as Arbutus Biopharma and Arcturus Therapeutics, offer non-viral, non-cell-targeted approaches that mainly exhibit liver trophism. In more recent years, startups such as Sixfold Bio, GenEdit, and Spotlight Therapeutics have begun to solve the non-viral gene delivery problem. Non-viral techniques offer the possibility of repeat dosing and greater tailorability of genetic payloads, which in the future will be more likely to take over viral-based delivery systems.

Companies such as Editas Medicine, Intellia Therapeutics, CRISPR Therapeutics, Casebia, Cellectis, Precision Biosciences, bluebird bio, and Sangamo have developed non-viral gene editing techniques, however frequently still use viruses for delivering gene insertion material following genomic cleavage by guided nucleases. These companies focus on gene editing, and still face major delivery hurdles.

BioNTech, Moderna Therapeutics and CureVac focus on delivery of mRNA payloads, which are necessarily non-viral delivery problems.

Alnylam, Dicerna Pharmaceuticals, and Ionis Pharmaceuticals focus on delivery of siRNA (antisense oligonucleotides) for gene suppression, which also necessitate non-viral delivery systems.

In academic contexts, a number of laboratories are working on delivery of PEGylated particles, which form serum protein coronas and chiefly exhibit LDL receptor mediated uptake in cells in vivo.[57]

In in vivo gene therapy, a vector (typically, a virus) is introduced to the patient, which then achieves the desired biological effect by passing the genetic material (e.g. for a missing protein) into the patient's cells. In ex vivo gene therapies, such as CAR-T therapeutics, the patient's own cells (autologous) or healthy donor cells (allogeneic) are modified outside the body (hence, ex vivo) using a vector to express a particular protein, such as a chimeric antigen receptor.[58]

In vivo gene therapy is seen as simpler, since it does not require the harvesting of mitotic cells. However, ex vivo gene therapies are better tolerated and less associated with severe immune responses.[59] The death of Jesse Gelsinger in a trial of an adenovirus-vectored treatment for ornithine transcarbamylase deficiency due to a systemic inflammatory reaction led to a temporary halt on gene therapy trials across the United States.[60] As of 2021[update], in vivo and ex vivo therapeutics are both seen as safe.[61]

Athletes may adopt gene therapy technologies to improve their performance.[62] Gene doping is not known to occur, but multiple gene therapies may have such effects. Kayser et al. argue that gene doping could level the playing field if all athletes receive equal access. Critics claim that any therapeutic intervention for non-therapeutic/enhancement purposes compromises the ethical foundations of medicine and sports.[63]

Genetic engineering could be used to cure diseases, but also to change physical appearance, metabolism, and even improve physical capabilities and mental faculties such as memory and intelligence. Ethical claims about germline engineering include beliefs that every fetus has a right to remain genetically unmodified, that parents hold the right to genetically modify their offspring, and that every child has the right to be born free of preventable diseases.[64][65][66] For parents, genetic engineering could be seen as another child enhancement technique to add to diet, exercise, education, training, cosmetics, and plastic surgery.[67][68] Another theorist claims that moral concerns limit but do not prohibit germline engineering.[69]

A recent issue of the journal Bioethics was devoted to moral issues surrounding germline genetic engineering in people.[70]

Possible regulatory schemes include a complete ban, provision to everyone, or professional self-regulation. The American Medical Association's Council on Ethical and Judicial Affairs stated that "genetic interventions to enhance traits should be considered permissible only in severely restricted situations: (1) clear and meaningful benefits to the fetus or child; (2) no trade-off with other characteristics or traits; and (3) equal access to the genetic technology, irrespective of income or other socioeconomic characteristics."[71]

As early in the history of biotechnology as 1990, there have been scientists opposed to attempts to modify the human germline using these new tools,[72] and such concerns have continued as technology progressed.[73][74] With the advent of new techniques like CRISPR, in March 2015 a group of scientists urged a worldwide moratorium on clinical use of gene editing technologies to edit the human genome in a way that can be inherited.[75][76][77][78] In April 2015, researchers sparked controversy when they reported results of basic research to edit the DNA of non-viable human embryos using CRISPR.[79][80] A committee of the American National Academy of Sciences and National Academy of Medicine gave qualified support to human genome editing in 2017[81][82] once answers have been found to safety and efficiency problems "but only for serious conditions under stringent oversight."[83]

Gene therapy approaches to replace a faulty gene with a healthy gene have been proposed and are being studied for treating some genetic diseases. Diseases such as sickle cell disease that are caused by autosomal recessive disorders for which a person's normal phenotype or cell function may be restored in cells that have the disease by a normal copy of the gene that is mutated, may be a good candidate for gene therapy treatment.[84][85] The risks and benefits related to gene therapy for sickle cell disease are not known.[85]

Some genetic therapies have been approved by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and for use in Russia and China.

Some of the unsolved problems include:

Three patients' deaths have been reported in gene therapy trials, putting the field under close scrutiny. The first was that of Jesse Gelsinger, who died in 1999, because of immune rejection response.[109][110] One X-SCID patient died of leukemia in 2003.[17] In 2007, a rheumatoid arthritis patient died from an infection; the subsequent investigation concluded that the death was not related to gene therapy.[111]

Regulations covering genetic modification are part of general guidelines about human-involved biomedical research.[citation needed] There are no international treaties which are legally binding in this area, but there are recommendations for national laws from various bodies.[citation needed]

The Helsinki Declaration (Ethical Principles for Medical Research Involving Human Subjects) was amended by the World Medical Association's General Assembly in 2008. This document provides principles physicians and researchers must consider when involving humans as research subjects. The Statement on Gene Therapy Research initiated by the Human Genome Organization (HUGO) in 2001, provides a legal baseline for all countries. HUGO's document emphasizes human freedom and adherence to human rights, and offers recommendations for somatic gene therapy, including the importance of recognizing public concerns about such research.[112]

No federal legislation lays out protocols or restrictions about human genetic engineering. This subject is governed by overlapping regulations from local and federal agencies, including the Department of Health and Human Services, the FDA and NIH's Recombinant DNA Advisory Committee. Researchers seeking federal funds for an investigational new drug application, (commonly the case for somatic human genetic engineering,) must obey international and federal guidelines for the protection of human subjects.[113]

NIH serves as the main gene therapy regulator for federally funded research. Privately funded research is advised to follow these regulations. NIH provides funding for research that develops or enhances genetic engineering techniques and to evaluate the ethics and quality in current research. The NIH maintains a mandatory registry of human genetic engineering research protocols that includes all federally funded projects.[114]

An NIH advisory committee published a set of guidelines on gene manipulation.[115] The guidelines discuss lab safety as well as human test subjects and various experimental types that involve genetic changes. Several sections specifically pertain to human genetic engineering, including Section III-C-1. This section describes required review processes and other aspects when seeking approval to begin clinical research involving genetic transfer into a human patient.[116] The protocol for a gene therapy clinical trial must be approved by the NIH's Recombinant DNA Advisory Committee prior to any clinical trial beginning; this is different from any other kind of clinical trial.[115]

As with other kinds of drugs, the FDA regulates the quality and safety of gene therapy products and supervises how these products are used clinically. Therapeutic alteration of the human genome falls under the same regulatory requirements as any other medical treatment. Research involving human subjects, such as clinical trials, must be reviewed and approved by the FDA and an Institutional Review Board.[117][118]

In 1972, Friedmann and Roblin authored a paper in Science titled "Gene therapy for human genetic disease?".[119] Rogers (1970) was cited for proposing that exogenous good DNA be used to replace the defective DNA in those with genetic defects.[120]

In 1984, a retrovirus vector system was designed that could efficiently insert foreign genes into mammalian chromosomes.[121]

The first approved gene therapy clinical research in the US took place on 14 September 1990, at the National Institutes of Health (NIH), under the direction of William French Anderson.[122] Four-year-old Ashanti DeSilva received treatment for a genetic defect that left her with adenosine deaminase deficiency (ADA-SCID), a severe immune system deficiency. The defective gene of the patient's blood cells was replaced by the functional variant. Ashanti's immune system was partially restored by the therapy. Production of the missing enzyme was temporarily stimulated, but the new cells with functional genes were not generated. She led a normal life only with the regular injections performed every two months. The effects were successful, but temporary.[123]

Cancer gene therapy was introduced in 1992/93 (Trojan et al. 1993).[124] The treatment of glioblastoma multiforme, the malignant brain tumor whose outcome is always fatal, was done using a vector expressing antisense IGF-I RNA (clinical trial approved by NIH protocol no.1602 24 November 1993,[125] and by the FDA in 1994). This therapy also represents the beginning of cancer immunogene therapy, a treatment which proves to be effective due to the anti-tumor mechanism of IGF-I antisense, which is related to strong immune and apoptotic phenomena.

In 1992, Claudio Bordignon, working at the Vita-Salute San Raffaele University, performed the first gene therapy procedure using hematopoietic stem cells as vectors to deliver genes intended to correct hereditary diseases.[126] In 2002, this work led to the publication of the first successful gene therapy treatment for ADA-SCID. The success of a multi-center trial for treating children with SCID (severe combined immune deficiency or "bubble boy" disease) from 2000 and 2002, was questioned when two of the ten children treated at the trial's Paris center developed a leukemia-like condition. Clinical trials were halted temporarily in 2002, but resumed after regulatory review of the protocol in the US, the United Kingdom, France, Italy, and Germany.[127]

In 1993, Andrew Gobea was born with SCID following prenatal genetic screening. Blood was removed from his mother's placenta and umbilical cord immediately after birth, to acquire stem cells. The allele that codes for adenosine deaminase (ADA) was obtained and inserted into a retrovirus. Retroviruses and stem cells were mixed, after which the viruses inserted the gene into the stem cell chromosomes. Stem cells containing the working ADA gene were injected into Andrew's blood. Injections of the ADA enzyme were also given weekly. For four years T cells (white blood cells), produced by stem cells, made ADA enzymes using the ADA gene. After four years more treatment was needed.[128]

Jesse Gelsinger's death in 1999 impeded gene therapy research in the US.[129][130] As a result, the FDA suspended several clinical trials pending the reevaluation of ethical and procedural practices.[131]

The modified gene therapy strategy of antisense IGF-I RNA (NIH n 1602)[125] using antisense / triple helix anti-IGF-I approach was registered in 2002, by Wiley gene therapy clinical trial - n 635 and 636. The approach has shown promising results in the treatment of six different malignant tumors: glioblastoma, cancers of liver, colon, prostate, uterus, and ovary (Collaborative NATO Science Programme on Gene Therapy USA, France, Poland n LST 980517 conducted by J. Trojan) (Trojan et al., 2012). This anti-gene antisense/triple helix therapy has proven to be efficient, due to the mechanism stopping simultaneously IGF-I expression on translation and transcription levels, strengthening anti-tumor immune and apoptotic phenomena.

Sickle cell disease can be treated in mice.[132] The mice which have essentially the same defect that causes human cases used a viral vector to induce production of fetal hemoglobin (HbF), which normally ceases to be produced shortly after birth. In humans, the use of hydroxyurea to stimulate the production of HbF temporarily alleviates sickle cell symptoms. The researchers demonstrated this treatment to be a more permanent means to increase therapeutic HbF production.[133]

A new gene therapy approach repaired errors in messenger RNA derived from defective genes. This technique has the potential to treat thalassaemia, cystic fibrosis and some cancers.[134]

Researchers created liposomes 25 nanometers across that can carry therapeutic DNA through pores in the nuclear membrane.[135]

In 2003, a research team inserted genes into the brain for the first time. They used liposomes coated in a polymer called polyethylene glycol, which unlike viral vectors, are small enough to cross the bloodbrain barrier.[136]

Short pieces of double-stranded RNA (short, interfering RNAs or siRNAs) are used by cells to degrade RNA of a particular sequence. If a siRNA is designed to match the RNA copied from a faulty gene, then the abnormal protein product of that gene will not be produced.[137]

Gendicine is a cancer gene therapy that delivers the tumor suppressor gene p53 using an engineered adenovirus. In 2003, it was approved in China for the treatment of head and neck squamous cell carcinoma.[34]

In March, researchers announced the successful use of gene therapy to treat two adult patients for X-linked chronic granulomatous disease, a disease which affects myeloid cells and damages the immune system. The study is the first to show that gene therapy can treat the myeloid system.[138]

In May, a team reported a way to prevent the immune system from rejecting a newly delivered gene.[139] Similar to organ transplantation, gene therapy has been plagued by this problem. The immune system normally recognizes the new gene as foreign and rejects the cells carrying it. The research utilized a newly uncovered network of genes regulated by molecules known as microRNAs. This natural function selectively obscured their therapeutic gene in immune system cells and protected it from discovery. Mice infected with the gene containing an immune-cell microRNA target sequence did not reject the gene.

In August, scientists successfully treated metastatic melanoma in two patients using killer T cells genetically retargeted to attack the cancer cells.[140]

In November, researchers reported on the use of VRX496, a gene-based immunotherapy for the treatment of HIV that uses a lentiviral vector to deliver an antisense gene against the HIV envelope. In a phase I clinical trial, five subjects with chronic HIV infection who had failed to respond to at least two antiretroviral regimens were treated. A single intravenous infusion of autologous CD4 T cells genetically modified with VRX496 was well tolerated. All patients had stable or decreased viral load; four of the five patients had stable or increased CD4 T cell counts. All five patients had stable or increased immune response to HIV antigens and other pathogens. This was the first evaluation of a lentiviral vector administered in a US human clinical trial.[141][142]

In May, researchers announced the first gene therapy trial for inherited retinal disease. The first operation was carried out on a 23-year-old British male, Robert Johnson, in early 2007.[143]

Leber's congenital amaurosis is an inherited blinding disease caused by mutations in the RPE65 gene. The results of a small clinical trial in children were published in April.[5] Delivery of recombinant adeno-associated virus (AAV) carrying RPE65 yielded positive results. In May, two more groups reported positive results in independent clinical trials using gene therapy to treat the condition. In all three clinical trials, patients recovered functional vision without apparent side-effects.[5][21][22][23]

In September researchers were able to give trichromatic vision to squirrel monkeys.[144] In November 2009, researchers halted a fatal genetic disorder called adrenoleukodystrophy in two children using a lentivirus vector to deliver a functioning version of ABCD1, the gene that is mutated in the disorder.[145]

An April paper reported that gene therapy addressed achromatopsia (color blindness) in dogs by targeting cone photoreceptors. Cone function and day vision were restored for at least 33 months in two young specimens. The therapy was less efficient for older dogs.[146]

In September it was announced that an 18-year-old male patient in France with beta thalassemia major had been successfully treated.[147] Beta thalassemia major is an inherited blood disease in which beta haemoglobin is missing and patients are dependent on regular lifelong blood transfusions.[148] The technique used a lentiviral vector to transduce the human -globin gene into purified blood and marrow cells obtained from the patient in June 2007.[149] The patient's haemoglobin levels were stable at 9 to 10 g/dL. About a third of the hemoglobin contained the form introduced by the viral vector and blood transfusions were not needed.[149][150] Further clinical trials were planned.[151] Bone marrow transplants are the only cure for thalassemia, but 75% of patients do not find a matching donor.[150]

Cancer immunogene therapy using modified antigene, antisense/triple helix approach was introduced in South America in 2010/11 in La Sabana University, Bogota (Ethical Committee 14 December 2010, no P-004-10). Considering the ethical aspect of gene diagnostic and gene therapy targeting IGF-I, the IGF-I expressing tumors i.e. lung and epidermis cancers were treated (Trojan et al. 2016).[152][153]

In 2007 and 2008, a man (Timothy Ray Brown) was cured of HIV by repeated hematopoietic stem cell transplantation (see also allogeneic stem cell transplantation, allogeneic bone marrow transplantation, allotransplantation) with double-delta-32 mutation which disables the CCR5 receptor. This cure was accepted by the medical community in 2011.[154] It required complete ablation of existing bone marrow, which is very debilitating.[155]

In August two of three subjects of a pilot study were confirmed to have been cured from chronic lymphocytic leukemia (CLL). The therapy used genetically modified T cells to attack cells that expressed the CD19 protein to fight the disease.[29] In 2013, the researchers announced that 26 of 59 patients had achieved complete remission and the original patient had remained tumor-free.[156]

Human HGF plasmid DNA therapy of cardiomyocytes is being examined as a potential treatment for coronary artery disease as well as treatment for the damage that occurs to the heart after myocardial infarction.[157][158]

In 2011, Neovasculgen was registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease, including critical limb ischemia; it delivers the gene encoding for VEGF.[35] Neovasculogen is a plasmid encoding the CMV promoter and the 165 amino acid form of VEGF.[159][160]

The FDA approved Phase I clinical trials on thalassemia major patients in the US for 10 participants in July.[161] The study was expected to continue until 2015.[151]

In July 2012, the European Medicines Agency recommended approval of a gene therapy treatment for the first time in either Europe or the United States. The treatment used Alipogene tiparvovec (Glybera) to compensate for lipoprotein lipase deficiency, which can cause severe pancreatitis.[162] The recommendation was endorsed by the European Commission in November 2012,[20][36][163][164] and commercial rollout began in late 2014.[165] Alipogene tiparvovec was expected to cost around $1.6 million per treatment in 2012,[166] revised to $1 million in 2015,[167] making it the most expensive medicine in the world at the time.[168] As of 2016[update], only the patients treated in clinical trials and a patient who paid the full price for treatment have received the drug.[169]

In December 2012, it was reported that 10 of 13 patients with multiple myeloma were in remission "or very close to it" three months after being injected with a treatment involving genetically engineered T cells to target proteins NY-ESO-1 and LAGE-1, which exist only on cancerous myeloma cells.[31]

In March researchers reported that three of five adult subjects who had acute lymphocytic leukemia (ALL) had been in remission for five months to two years after being treated with genetically modified T cells which attacked cells with CD19 genes on their surface, i.e. all B cells, cancerous or not. The researchers believed that the patients' immune systems would make normal T cells and B cells after a couple of months. They were also given bone marrow. One patient relapsed and died and one died of a blood clot unrelated to the disease.[30]

Following encouraging Phase I trials, in April, researchers announced they were starting Phase II clinical trials (called CUPID2 and SERCA-LVAD) on 250 patients[170] at several hospitals to combat heart disease. The therapy was designed to increase the levels of SERCA2, a protein in heart muscles, improving muscle function.[171] The U.S. Food and Drug Administration (FDA) granted this a breakthrough therapy designation to accelerate the trial and approval process.[172] In 2016, it was reported that no improvement was found from the CUPID 2 trial.[173]

In July researchers reported promising results for six children with two severe hereditary diseases had been treated with a partially deactivated lentivirus to replace a faulty gene and after 732 months. Three of the children had metachromatic leukodystrophy, which causes children to lose cognitive and motor skills.[174] The other children had WiskottAldrich syndrome, which leaves them to open to infection, autoimmune diseases, and cancer.[175] Follow up trials with gene therapy on another six children with WiskottAldrich syndrome were also reported as promising.[176][177]

In October researchers reported that two children born with adenosine deaminase severe combined immunodeficiency disease (ADA-SCID) had been treated with genetically engineered stem cells 18 months previously and that their immune systems were showing signs of full recovery. Another three children were making progress.[27] In 2014, a further 18 children with ADA-SCID were cured by gene therapy.[178] ADA-SCID children have no functioning immune system and are sometimes known as "bubble children".[27]

Also in October researchers reported that they had treated six people with haemophilia in early 2011 using an adeno-associated virus. Over two years later all six were producing clotting factor.[27][179]

In January researchers reported that six choroideremia patients had been treated with adeno-associated virus with a copy of REP1. Over a six-month to two-year period all had improved their sight.[6][180] By 2016, 32 patients had been treated with positive results and researchers were hopeful the treatment would be long-lasting.[24] Choroideremia is an inherited genetic eye disease with no approved treatment, leading to loss of sight.

In March researchers reported that 12 HIV patients had been treated since 2009 in a trial with a genetically engineered virus with a rare mutation (CCR5 deficiency) known to protect against HIV with promising results.[181][182]

Clinical trials of gene therapy for sickle cell disease were started in 2014.[183][184]

In February LentiGlobin BB305, a gene therapy treatment undergoing clinical trials for treatment of beta thalassemia gained FDA "breakthrough" status after several patients were able to forgo the frequent blood transfusions usually required to treat the disease.[185]

In March researchers delivered a recombinant gene encoding a broadly neutralizing antibody into monkeys infected with simian HIV; the monkeys' cells produced the antibody, which cleared them of HIV. The technique is named immunoprophylaxis by gene transfer (IGT). Animal tests for antibodies to ebola, malaria, influenza, and hepatitis were underway.[186][187]

In March, scientists, including an inventor of CRISPR, Jennifer Doudna, urged a worldwide moratorium on germline gene therapy, writing "scientists should avoid even attempting, in lax jurisdictions, germline genome modification for clinical application in humans" until the full implications "are discussed among scientific and governmental organizations".[75][76][77][78]

In December, scientists of major world academies called for a moratorium on inheritable human genome edits, including those related to CRISPR-Cas9 technologies[188] but that basic research including embryo gene editing should continue.[189]

Researchers successfully treated a boy with epidermolysis bullosa using skin grafts grown from his own skin cells, genetically altered to repair the mutation that caused his disease.[190]

In November, researchers announced that they had treated a baby girl, Layla Richards, with an experimental treatment using donor T cells genetically engineered using TALEN to attack cancer cells. One year after the treatment she was still free of her cancer (a highly aggressive form of acute lymphoblastic leukaemia [ALL]).[191] Children with highly aggressive ALL normally have a very poor prognosis and Layla's disease had been regarded as terminal before the treatment.[192][193]

In April the Committee for Medicinal Products for Human Use of the European Medicines Agency endorsed a gene therapy treatment called Strimvelis[194][195] and the European Commission approved it in June.[196] This treats children born with adenosine deaminase deficiency and who have no functioning immune system. This was the second gene therapy treatment to be approved in Europe.[197]

In October, Chinese scientists reported they had started a trial to genetically modify T cells from 10 adult patients with lung cancer and reinject the modified T cells back into their bodies to attack the cancer cells. The T cells had the PD-1 protein (which stops or slows the immune response) removed using CRISPR-Cas9.[198][199]

A 2016 Cochrane systematic review looking at data from four trials on topical cystic fibrosis transmembrane conductance regulator (CFTR) gene therapy does not support its clinical use as a mist inhaled into the lungs to treat cystic fibrosis patients with lung infections. One of the four trials did find weak evidence that liposome-based CFTR gene transfer therapy may lead to a small respiratory improvement for people with CF. This weak evidence is not enough to make a clinical recommendation for routine CFTR gene therapy.[200]

In February Kite Pharma announced results from a clinical trial of CAR-T cells in around a hundred people with advanced non-Hodgkin lymphoma.[201]

In March, French scientists reported on clinical research of gene therapy to treat sickle cell disease.[202]

In August, the FDA approved tisagenlecleucel for acute lymphoblastic leukemia.[203] Tisagenlecleucel is an adoptive cell transfer therapy for B-cell acute lymphoblastic leukemia; T cells from a person with cancer are removed, genetically engineered to make a specific T-cell receptor (a chimeric T cell receptor, or "CAR-T") that reacts to the cancer, and are administered back to the person. The T cells are engineered to target a protein called CD19 that is common on B cells. This is the first form of gene therapy to be approved in the United States. In October, a similar therapy called axicabtagene ciloleucel was approved for non-Hodgkin lymphoma.[204]

In October, biophysicist and biohacker Josiah Zayner claimed to have performed the very first in-vivo human genome editing in the form of a self-administered therapy.[205][206]

On 13 November, medical scientists working with Sangamo Therapeutics, headquartered in Richmond, California, announced the first ever in-body human gene editing therapy.[207][208] The treatment, designed to permanently insert a healthy version of the flawed gene that causes Hunter syndrome, was given to 44-year-old Brian Madeux and is part of the world's first study to permanently edit DNA inside the human body.[209] The success of the gene insertion was later confirmed.[210][211] Clinical trials by Sangamo involving gene editing using zinc finger nuclease (ZFN) are ongoing.[212]

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FDA approves first cancer treatment for any solid tumor with a specific …

For Immediate Release: May 23, 2017

The U.S. Food and Drug Administration today granted accelerated approval to a treatment for patients whose cancers have a specific genetic feature (biomarker). This is the first time the agency has approved a cancer treatment based on a common biomarker rather than the location in the body where the tumor originated.

Keytruda (pembrolizumab) is indicated for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having a biomarker referred to as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). This indication covers patients with solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options and patients with colorectal cancer that has progressed following treatment with certain chemotherapy drugs.

This is an important first for the cancer community, said Richard Pazdur, M.D., acting director of the Office of Hematology and Oncology Products in the FDAs Center for Drug Evaluation and Research and director of the FDAs Oncology Center of Excellence. Until now, the FDA has approved cancer treatments based on where in the body the cancer startedfor example, lung or breast cancers. We have now approved a drug based on a tumors biomarker without regard to the tumors original location.

MSI-H and dMMR tumors contain abnormalities that affect the proper repair of DNA inside the cell. Tumors with these biomarkers are most commonly found in colorectal, endometrial and gastrointestinal cancers, but also less commonly appear in cancers arising in the breast, prostate, bladder, thyroid gland and other places. Approximately 5 percent of patients with metastatic colorectal cancer have MSI-H or dMMR tumors.

Keytruda works by targeting the cellular pathway known as PD-1/PD-L1 (proteins found on the bodys immune cells and some cancer cells). By blocking this pathway, Keytruda may help the bodys immune system fight the cancer cells. The FDA previously approved Keytruda for the treatment of certain patients with metastatic melanoma, metastatic non-small cell lung cancer, recurrent or metastatic head and neck cancer, refractory classical Hodgkin lymphoma, and urothelial carcinoma.

Keytruda was approved for this new indication using the Accelerated Approval pathway, under which the FDA may approve drugs for serious conditions where there is unmet medical need and a drug is shown to have certain effects that are reasonably likely to predict a clinical benefit to patients. Further study is required to verify and describe anticipated clinical benefits of Keytruda, and the sponsor is currently conducting these studies in additional patients with MSI-H or dMMR tumors.

The safety and efficacy of Keytruda for this indication were studied in patients with MSI-H or dMMR solid tumors enrolled in one of five uncontrolled, single-arm clinical trials. In some trials, patients were required to have MSI-H or dMMR cancers, while in other trials, a subgroup of patients were identified as having MSI-H or dMMR cancers by testing tumor samples after treatment began. A total of 15 cancer types were identified among 149 patients enrolled across these five clinical trials. The most common cancers were colorectal, endometrial and other gastrointestinal cancers. The review of Keytruda for this indication was based on the percentage of patients who experienced complete or partial shrinkage of their tumors (overall response rate) and for how long (durability of response). Of the 149 patients who received Keytruda in the trials, 39.6 percent had a complete or partial response. For 78 percent of those patients, the response lasted for six months or more.

Common side effects of Keytruda include fatigue, itchy skin (pruritus), diarrhea, decreased appetite, rash, fever (pyrexia), cough, difficulty breathing (dyspnea), musculoskeletal pain, constipation and nausea. Keytruda can cause serious conditions known as immune-mediated side effects, including inflammation of healthy organs such as the lungs (pneumonitis), colon (colitis), liver (hepatitis), endocrine glands (endocrinopathies) and kidneys (nephritis). Complications or death related to allogeneic hematopoietic stem cell transplantation after using Keytruda has occurred.

Patients who experience severe or life-threatening infusion-related reactions should stop taking Keytruda. Women who are pregnant or breastfeeding should not take Keytruda because it may cause harm to a developing fetus or newborn baby. The safety and effectiveness of Keytruda in pediatric patients with MSI-H central nervous system cancers have not been established.

The FDA granted this application Priority Review designation, under which the FDAs goal is to take action on an application within six months where the agency determines that the drug, if approved, would significantly improve the safety or effectiveness of treating, diagnosing or preventing a serious condition.

The FDA granted accelerated approval of Keytruda to Merck & Co.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nations food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

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BioMarin Resubmits Biologics License Application (BLA) for Valoctocogene Roxaparvovec AAV Gene Therapy for Severe Hemophilia A to the FDA – Investor…

BioMarin Resubmits Biologics License Application (BLA) for Valoctocogene Roxaparvovec AAV Gene Therapy for Severe Hemophilia A to the FDA

BLA Includes Substantial Body of Data from Pivotal Phase 3 and Ongoing Phase 1/2 Studies

If Approved, Would Be 1st Gene Therapy in U.S. for Treatment of Severe Hemophilia A

SAN RAFAEL, Calif., Sept. 29, 2022 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) announced today that the Company resubmitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for its investigational AAV gene therapy, valoctocogene roxaparvovec, for adults with severe hemophilia A. The resubmission incorporates the Company's response to the FDA Complete Response (CR) Letter for valoctocogene roxaparvovec gene therapy issued on August 18, 2020, and subsequent feedback, including two-year outcomes from the global GENEr8-1 Phase 3 study and supportive data from five years of follow-up from the ongoing Phase 1/2 dose escalation study.

BioMarin anticipates an FDA response by the end of October on whether the BLA resubmission is complete and acceptable for review. Typically, BLA resubmissions are followed by a six-month review procedure. However, the Company anticipates three additional months of review may be necessary based on the number of data read-outs that will emerge during the procedure. If approved, valoctocogene roxaparvovec would be the first commercially-available gene therapy in the U.S. for the treatment of severe hemophilia A.

The FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to valoctocogene roxaparvovec in March 2021. RMAT is an expedited program intended to facilitate development and review of regenerative medicine therapies, such as valoctocogene roxaparvovec, that are expected to address an unmet medical need in patients with serious conditions. The RMAT designation is complementary to Breakthrough Therapy Designation, which the Company received for valoctocogene roxaparvovec in 2017.

In addition to the RMAT Designation and Breakthrough Therapy Designation, BioMarin's valoctocogene roxaparvovec also received orphan drug designation from the EMA and FDA for the treatment of severe hemophilia A. Orphan drug designation is reserved for medicines treating rare, life-threatening or chronically debilitating diseases. The European Commission (EC) granted conditional marketing authorization to valoctocogene roxaparvovec gene therapy under the brand name ROCTAVIAN on August 24, 2022 and endorsed the recommendation from the European Medicines Agency (EMA) to maintain orphan drug designation, thereby granting a 10-year period of market exclusivity in the European Union.

"We are pleased to reach this point in the development program for valoctocogene roxaparvovec and look forward to working with the FDA with the goal of bringing a potentially transformative therapy to people with severe hemophilia A in the United States," said Hank Fuchs, M.D., President of Worldwide Research and Development at BioMarin. "This large and robust data set provided in this BLA resubmission shows an encouraging efficacy profile. We remain committed to sharing these data with the public, along with even longer-term data generated through our ongoing clinical trials and any post-approval studies, to further our understanding of AAV gene therapy in severe hemophilia A and of gene therapies more broadly."

The resubmission includes a substantial body of data from the valoctocogene roxaparvovec clinical development program, the most extensively studied gene therapy for severe hemophilia A, including two-year outcomes from the global GENEr8-1 Phase 3 study. The GENEr8-1 Phase 3 study demonstrated stable and durable bleed control, including a reduction in the mean annualized bleeding rate (ABR) and the mean annualized Factor VIII infusion rate. In addition, the data package included supportive evidence from five years of follow-up from the 6e13 vg/kg dose cohort in the ongoing Phase 1/2 dose escalation study. The resubmission alsoincludesaproposedlong-term extension studyfollowingall clinicaltrialparticipantsfor up to 15years, as well astwo post-approval registry studies.

Robust Clinical Program

BioMarin has multiple clinical studies underway in its comprehensive gene therapy program for the treatment of severe hemophilia A. In addition to the global Phase 3 study GENEr8-1 and the ongoing Phase 1/2 dose escalation study, the Company is also conducting a Phase 3, single arm, open-label study to evaluate the efficacy and safety of valoctocogene roxaparvovec at a dose of 6e13 vg/kg with prophylactic corticosteroids in people with severe hemophilia A (Study 270-303). Also ongoing are a Phase 1/2 Study with the 6e13 vg/kg dose of valoctocogene roxaparvovec in people with severe hemophilia A with pre-existing AAV5 antibodies (Study 270-203) and a Phase 1/2 Study with the 6e13 vg/kg dose of valoctocogene roxaparvovec in people with severe hemophilia A with active or prior Factor VIII inhibitors (Study 270-205).

Safety Summary

Overall, to date, a single 6e13 vg/kg dose of valoctocogene roxaparvovec has been well tolerated with no delayed-onset treatment related adverse events. The most common adverse events (AE) associated with valoctocogene roxaparvovec have occurred early and included transient infusion associated reactions and mild to moderate rise in liver enzymes with no long-lasting clinical sequelae. Alanine aminotransferase (ALT) elevation, a laboratory test of liver function, has remained the most common adverse drug reaction. Other adverse reactions have included aspartate aminotransferase (AST) elevation (101 participants, 63%), nausea (55 participants, 34%), headache (54 participants, 34%), and fatigue (44 participants, 28%). No participants have developed inhibitors to Factor VIII, thromboembolic events or malignancy associated with valoctocogene roxaparvovec.

About Hemophilia A

People living with hemophilia A lack sufficient functioning Factor VIII protein to help their blood clot and are at risk for painful and/or potentially life-threatening bleeds from even modest injuries. Additionally, people with the most severe form of hemophilia A (Factor VIII levels <1%) often experience painful, spontaneous bleeds into their muscles or joints. Individuals with the most severe form of hemophilia A make up approximately 50 percent of the hemophilia A population. People with hemophilia A with moderate (Factor VIII 1-5%) or mild (Factor VIII 5-40%) disease show a much-reduced propensity to bleed. Individuals with severe hemophilia A are treated with a prophylactic regimen of intravenous Factor VIII infusions administered 2-3 times per week (100-150 infusions per year) or a bispecific monoclonal antibody that mimics the activity of Factor VIII administered 1-4 times per month (12-48 injections or shots per year). Despite these regimens, many people continue to experience breakthrough bleeds, resulting in progressive and debilitating joint damage, which can have a major impact on their quality of life.

Hemophilia A, also called Factor VIII deficiency or classic hemophilia, is an X-linked genetic disorder caused by missing or defective Factor VIII, a clotting protein. Although it is passed down from parents to children, about 1/3 of cases are caused by a spontaneous mutation, a new mutation that was not inherited. Approximately 1 in 10,000 people have hemophilia A.

About BioMarin

BioMarin is a global biotechnology company that develops and commercializes innovative therapies for people with serious and life-threatening genetic diseases and medical conditions. The Company selects product candidates for diseases and conditions that represent a significant unmet medical need, have well-understood biology and provide an opportunity to be first-to-market or offer a significant benefit over existing products. The Company's portfolio consists of eight commercial products and multiple clinical and preclinical product candidates for the treatment of various diseases. For additional information, please visitwww.biomarin.com.

Forward-Looking Statements

This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc. (BioMarin), including without limitation, statements about: BioMarin anticipating an FDA response by the end of October on whether the BLA resubmission is complete and acceptable for review, BioMarin's expectations regarding the duration of the review procedure, valoctocogene roxaparvovec being the first commercially-available gene therapy in the U.S. for the treatment of severe hemophilia A, if approved, BioMarin's commitment to sharing longer-term data generated through its ongoing clinical trials and any post-approval studies. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others: the results and timing of current and planned preclinical studies and clinical trials of valoctocogene roxaparvovec; additional data from the continuation of the clinical trials of valoctocogene roxaparvovec, any potential adverse events observed in the continuing monitoring of the participants in the clinical trials; the content and timing of decisions by the FDA and other regulatory authorities, including decisions to grant additional marketing registrations based on an EMA license; the content and timing of decisions by local and central ethics committees regarding the clinical trials; our ability to successfully manufacture valoctocogene roxaparvovec for the clinical trials and commercially; and those and those factors detailed in BioMarin's filings with the Securities and Exchange Commission (SEC), including, without limitation, the factors contained under the caption "Risk Factors" in BioMarin's Quarterly Report on Form 10-Q for the quarter ended June 30, 2022 as such factors may be updated by any subsequent reports. Stockholders are urged not to place undue reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation to update or alter any forward-looking statement, whether as a result of new information, future events or otherwise.

BioMarin is a registered trademark of BioMarin Pharmaceutical Inc and ROCTAVIAN is a trademark of BioMarin Pharmaceutical Inc.

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BioMarin Resubmits Biologics License Application (BLA) for Valoctocogene Roxaparvovec AAV Gene Therapy for Severe Hemophilia A to the FDA - Investor...

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This gene therapy company is testing new tech to ‘switch off’ diabetes and obesity with a pill – Euronews

What if people who need regular injections to treat chronic diseases could instead take a pill that precisely controls the production of the right proteins and hormones inside their bodies?

A promising new gene therapy technology that aims to turn the human body into such a medicine-making factory could, if successful, push the boundaries of medicine and make certain treatments much more convenient and potentially less expensive.

MeiraGTx, a gene therapy company, is working to make this futuristic vision a reality.

The British company already develops traditional gene therapy, which replaces missing or broken genes in people with inherited disorders. That side of business is booming, and the firm just opened a manufacturing facility in Ireland that could employ up to 300 people.

But MeiraGTx is also making strides in what it calls gene regulation therapy, which it says could help control much more precisely the genes that instruct cells to make or stop making certain proteins.

Its no easy feat and the technology would take years to bring to market, but it has the potential to make gene therapy even more life-changing for patients.

When you put a gene or replace a missing gene into a cell today, you put the gene in and it is expressed for the rest of that cell's life, MeiraGTx CEO Alexandria Forbes told Euronews Next.

Its very hard to build a gene therapy that is switched on and off when it's needed, particularly in a disease. And what's even harder is to create a gene therapy which is switched on or off when you, the doctor or patient, want it to be.

MeiraGTx says it has developed a switch of this sort that could help make patients lives much easier: rather than injecting synthetic hormones and proteins into them, it could insert the gene that tells their body to make those, while a pill activates the gene only when the specific protein or hormone is needed.

Take Epogen (epoetin alfa) a well-known injectable drug that helps create more red blood cells when you're anaemic, with kidney disease or you're being treated for cancer.

What you can do, for example, is put the gene for Epogen into the body, into the muscle, and have a switching system that only allows your body to make the natural form of Epogen when you take a pill, Forbes explained.

So we don't have to make unnatural forms of these drugs because what we're doing is we're providing the body with the message to make the drug, and that message is only switched on when we give the body a pill.

MeiraGTx told Euronews Next it has already tested this technology in animals and is hoping to start trialling it on humans in 2023.

If successful, it could have huge, broad-ranging implications, Forbes said.

This isn't only for gene therapy. It allows you to control cell therapy, immuno-oncology, antibody production anything that is a protein or peptide that can be made by the body.

Many traditional drugs involve making a protein outside the body, like insulin to fight diabetes or antibodies to fight cancer. That protein is manufactured in cells or bacteria outside the body and then is injected into the body on a regular basis as a treatment.

Gene therapy, by contrast, involves putting into the body a gene encoding the therapeutic protein: rather than injecting the protein over and over and over again, you put the gene for the protein into the person and the protein is made in the person's body.

Gene therapies are typically used against inherited diseases, where a gene is missing or not functioning well. Gene therapy inserts into a patient a perfect copy of that gene to replace the missing or broken one.

So our drugs are actually genes - DNA - and they're delivered into the body by being encapsulated in viral proteins which act like a little spaceship and insert those genes that we've made into the appropriate cell, Forbes said.

This type of technology requires a very specific manufacturing process to ensure through rigorous testing that every single batch of these genes always has the same identical quality, safety and potency, she explained.

MeiraGTx controls this manufacturing in-house and has just inaugurated a new commercial-scale facility in Shannon, Ireland, thats set to employ 100 people initially and up to 300 as business grows.

The company hopes the new site will help accelerate its development and delivery of gene therapy treatments to patients with an initial focus on rare inherited disorders affecting the eye, central nervous system, and salivary gland.

But MeiraGTx argues that adding a switch to be able to fine-tune gene therapy has the potential to considerably expand this range to also tackle non-hereditary diseases that affect hundreds of millions of people worldwide, including heart disease, cancer and diabetes.

It says it could even help fight obesity, arguably one of the biggest global health challenges.

The causes behind obesity are complex and multi-faceted, genetic factors mean some people are more at risk than others, and the hormones that control appetite are very unstable and short-lasting.

A class of injectable diabetes drugs currently proving highly effective against obesity are GLP- 1 drugs, which help control blood sugar levels. But they work better in combination with several other gut peptides that affect metabolism.

The challenge, once again, is to precisely control the levels of these peptides.

MeiraGTx claims its technology may someday allow those hoping to lose weight to switch on the combination of genes that produce the hormones and peptides controlling their appetite, blood sugar levels and ultimately their fat.

We can now put the genes for three natural gut peptides that control metabolism into the body and give a pill when we want those drugs, Forbes said.

In theory, if clinical trials go well, the potential applications for other diseases are dizzying and they directly raise the question of extending human life expectancy. But that should not be the priority right now, Forbes said.

I think that currently we have really big problems with obesity, with Alzheimer's, with ways of living that mean we are young and living poorly, she said.

And these sorts of products can be used to help address those really large indications, not just the rare gene replacements.

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Atamyo Therapeutics Announces First Patient Dosed with ATA-100 Gene Therapy in LGMD-R9 Clinical Trial – Business Wire

EVRY, France--(BUSINESS WIRE)--Atamyo Therapeutics, a biotechnology company focused on the development of new-generation gene therapies targeting neuromuscular diseases, today announced the dosing with ATA-100 of a first patient in a phase 1/2 clinical study in FRKP-related limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9).

This is an exciting milestone for our company but most importantly, if this clinical trial is successful, it could have a life-changing impact for patients affected by LGMD-R9, said Stephane Degove, Chief Executive Officer and Co-Founder of Atamyo Therapeutics.

This clinical trial (EudraCT 2021-004276-33, NCT05224505) is a multicenter, Phase 1/2 study evaluating safety, pharmacodynamic, efficacy, and immunogenicity of intravenous ATA-100, a single-dose Adeno-Associated Virus (AAV) vector carrying the human FKRP transgene.

This study will consist of 2 phases: an open-label dose escalation phase (Stage 1) and a double-blind placebo controlled, randomized phase (Stage 2).

LGMD-R9 is a severe progressive and debilitating disease with no approved treatment, said Pr. John Vissing, Director of the Copenhagen Neuromuscular Center at the National Hospital, Rigshospitalet, in Copenhagen, where the first patient was dosed, and principal investigator of this trial. This experimental treatment represents a new hope for the patients. It is a great motivation to know that the work we are doing here has the potential to make a life-changing difference.

After the first patient dosed in Copenhagen, we are now expecting recruitments at the two other approved clinical sites (Paris, FR, and Newcastle, UK) to complete enrollment of the dose escalation phase (Stage 1) of the study. For Stage 2 (after dose selection), we plan to open additional clinical sites in Europe and in the United States, said Dr. Sophie Olivier, Chief Medical Officer of Atamyo.

About the LGMD-R9 program ATA-100

ATA-100 is a one-time gene replacement therapy for LGMD-R9/2I based on the research of Dr. Isabelle Richard, who heads the Progressive Muscular Dystrophies Laboratory at Genethon (UMR 951 INSERM/Genethon/UEVE). ATA-100 has been awarded Orphan Drug Designation status by the U.S. Food and Drug Administration and the European Medicines Agency.

LGMD2I/R9 is a rare genetic disease caused by mutations in the gene that produces fukutin-related protein (FKRP). It affects an estimated 5,000 people in the US and Europe. Symptoms appear around late childhood or early adulthood. Patients suffer from progressive muscular weakness leading to loss of ambulation. They also are prone to respiratory impairment and myocardial dysfunction. There are currently no curative treatments for LGMDR9.

About Atamyo Therapeutics

Atamyo Therapeutics is a clinical-stage biopharma focused on the development of a new generation of effective and safe gene therapies for neuromuscular diseases. A spin-off of gene therapy pioneer Genethon, Atamyo leverages unique expertise in AAV-based gene therapy and muscular dystrophies from the Progressive Muscular Dystrophies Laboratory at Genethon. Atamyos most advanced programs address different forms of limb-girdle muscular dystrophies (LGMD). The name of the company is derived from two words: Celtic Atao which means Always or Forever and Myo which is the Greek root for muscle. Atamyo conveys the spirit of its commitment to improve the life of patients affected by neuromuscular diseases with life-long efficient treatments. For more information visit http://www.atamyo.com

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Viral Vector Manufacturing, Non-Viral Vector Manufacturing and Gene Therapy Manufacturing Market by Scale of Operation, Type of Vector, Application…

New York, Sept. 29, 2022 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Viral Vector Manufacturing, Non-Viral Vector Manufacturing and Gene Therapy Manufacturing Market by Scale of Operation, Type of Vector, Application Area, Therapeutic Area, and Geographical Regions : Industry Trends and Global Forecasts, 2022-2035" - https://www.reportlinker.com/p06323417/?utm_source=GNW In fact, in 2021, cell and gene therapy developers raised capital worth more than USD 20 billion, registering an increase of 19% from the amount raised in 2020 (~USD 17 billion). It is worth highlighting that, in February 2022, the USFDA approved second CAR-T therapy, CARVYKTI, developed by Johnson and Johnson, which can be used for the treatment of relapsed or refractory multiple myeloma. Additionally, close to 1,500 clinical trials are being conducted, globally, for the evaluation of cell and gene therapies. Over time, it has been observed that the clinical success of these therapies relies on the design and type of gene delivery vector used (in therapy development and / or administration). At present, several innovator companies are actively engaged in the development / production of viral vectors and / or non-viral vectors for cell and gene therapies. In this context, it is worth mentioning that, over the past few years, multiple viral vector and non-viral vector based vaccine candidates have been developed against COVID-19 (caused by novel coronavirus, SARS-CoV-2) and oncological disorders; this is indicative of lucrative opportunities for companies that have the required capabilities to manufacture vectors and gene therapies.

The viral and non-viral vector manufacturing landscape features a mix of industry players (well-established companies, mid-sized firms and start-ups / small companies), as well as several academic institutes. It is worth highlighting that several companies that have the required capabilities and facilities to manufacturing vectors for both in-house requirements and offer contract services (primarily to ensure the optimum use of their resources and open up additional revenue generation opportunities) have emerged in this domain. Further, in order to produce more effective and affordable vectors, several stakeholders are integrating various novel technologies; these technologies are likely to improve the scalability and quality of the resultant therapy. In addition, this industry has also witnessed a significant increase in the partnership and expansion activities over the past few years, with several companies having been acquired by the larger firms. Given the growing demand for interventions that require genetic modification, the vector and gene therapy manufacturing market is poised to witness substantial growth in the foreseen future.

SCOPE OF THE REPORTThe Viral Vectors, Non-Viral Vectors and Gene Therapy Manufacturing Market (5th Edition) by Scale of Operation (Preclinical, Clinical and Commercial), Type of Vector (AAV Vector, Adenoviral Vector, Lentiviral Vector, Retroviral Vector, Plasmid DNA and Others), Application Area (Gene Therapy, Cell Therapy and Vaccine), Therapeutic Area (Oncological Disorders, Rare Disorders, Neurological Disorders, Sensory Disorders, Metabolic Disorders, Musco-skeletal Disorders, Blood Disorders, Immunological Diseases, and Others), and Geographical Regions (North America, Europe, Asia Pacific, MENA, Latin America and Rest of the World): Industry Trends and Global Forecasts, 2022-2035 report features an extensive study of the rapidly growing market of vector and gene therapy manufacturing, focusing on contract manufacturers, as well as companies having in-house manufacturing facilities. The study presents an in-depth analysis of the various firms / organizations that are engaged in this domain, across different regions of the globe. Amongst other elements, the report includes:An overview of the current status of the market with respect to the players engaged (both industry and non-industry) in the manufacturing of viral, non-viral and other novel types of vectors and gene therapies. It features information on the year of establishment, company size, location of headquarters, type of product manufactured (vector and gene therapy / cell therapy / vaccine), location of manufacturing facilities, type of manufacturers (in-house and contract services), scale of operation (preclinical, clinical and commercial), type of vector manufactured (AAV, adenoviral, lentiviral, retroviral, plasmid DNA and others) and application area (gene therapy, cell therapy, vaccine and others).An analysis of the technologies offered / developed by the companies enagaged in this domain, based on the type of technology (viral vector related platform, non-viral vector related platform and others), type of manufacturer (vector manufacturing, gene delivery, product manufacturing, transduction / transfection, vector packaging and other), scale of operation (preclinical, clinical and commercial), type of vector involved (AAV, adenoviral, lentiviral, retroviral, non-viral and other viral vectors), application area (gene therapy, cell therapy, vcaccine and others). It also highlights the most prominent players within this domain, in terms of number of technologies.A region-wise, company competitiveness analysis, highlighting key players engaged in the manufacturing of vectors and gene therapies, across key geographical areas, featuring a four-dimensional bubble representation, taking into consideration supplier strength (based on experience in this field), manufacturing strength (type of product manufactured, number of manufacturing facilites and number of application areas), service strength (scale of operation, number of vectors manufactured and geographical reach) and company size (small, mid-sized and large).Elaborate profiles of key players based in North America, Europe and Asia-Pacific (shortlisted based on proprietary criterion). Each profile features an overview of the company / organization, its financial performance (if available), information related to its manufacturing facilities, vector manufacturing technology and an informed future outlook.Tabulated profiles of the other key players headquartered in different regions across the globe (shortlisted based on proprietary criterion). Each profile features an overview of the company, its financial performance (if available), information related to its manufacturing capabilities, and an informed future outlook.An analysis of partnerships and collaborations established in this domain since 2015; it includes details of deals that were / are focused on the manufacturing of vectors, which were analyzed on the basis of year of partnership, type of partnership (manufacturing agreement, product / technology licensing, product development, merger / acqusition, research and development agreement, process development / optimization, service alliance, production asset / facility acquisition, supply agreement and others), scale of operation (preclinical, clinical and commercial), type of vector involved (AAV, adenoviral, lentiviral, retroviral, plasmid and others), region and most active players (in terms of number of partnerships).An analysis of the expansions related to viral vector and non-viral vector manufacturing, which have been undertaken since 2015, based on several parameters, such as year of expansion, type of expansion (new facility / plant establishment, facility expansion, technology installation / expansion, capacity expansion, service expansion and others), type of vector (AAV, adenoviral, lentiviral, retroviral, plasmid and others), application area (gene therapy, cell therapy, vaccine and others) and geographical location of the expansion.An analysis evaluating the potential strategic partners (comparing vector based therapy developers and vector purification product developers) for vector and gene therapy product manufacturers, based on several parameters, such as developer strength, product strength, type of vector, therapeutic area, pipeline strength (preclinical and clinical).An overview of other viral / non-viral gene delivery approaches that are currently being researched for the development of therapies involving genetic modification.An in-depth analysis of viral vector and plasmid DNA manufacturers, featuring three schematic representations, a three dimensional grid analysis, representing the distribution of vector manufacturers (on the basis of type of vector) across various scales of operation and type of manufacturer (in-house operations and contract manufacturing services), a heat map of viral vector and plasmid DNA manufacturers based on the type of vector (AAV, adenoviral vector, lentiviral vector, retroviral vector and plasmid DNA) and type of organization (industry (small, mid-sized and large) and non-industry), and a schematic world map representation, highlighting the headquarters and geographical location of key vector manufacturing hubs.An analysis of the various factors that are likely to influence the pricing of vectors, featuring different models / approaches that may be adopted by product developers / manufacturers in order to decide the prices of proprietary vectors.An estimate of the overall, installed vector manufacturing capacity of industry players based on the information available in the public domain, and insights generated via both secondary and primary research. The analysis also highlights the distribution of the global capacity by company size (small, mid-sized and large), scale of operation (clinical and commercial), type of vector (viral vector and plasmid DNA) and region (North America, Europe, Asia Pacific and the rest of the world).An informed estimate of the annual demand for viral and non-viral vectors, taking into account the marketed gene-based therapies and clinical studies evaluating vector-based therapies; the analysis also takes into consideration various relevant parameters, such as target patient population, dosing frequency and dose strength.A discussion on the factors driving the market and various challenges associated with the vector production process.A qualitative analysis, highlighting the five competitive forces prevalent in this domain, including threats for new entrants, bargaining power of drug developers, bargaining power of vector and gene therapy manufacturers, threats of substitute technologies and rivalry among existing competitors.

One of the key objectives of this report was to evaluate the current market size and the future opportunity associated with the vector and gene therapy manufacturing market, over the coming decade. Based on various parameters, such as the likely increase in number of clinical studies, anticipated growth in target patient population, existing price variations across different types of vectors, and the anticipated success of gene therapy products (considering both approved and late-stage clinical candidates), we have provided an informed estimate of the likely evolution of the market in the short to mid-term and long term, for the period 2022-2035. In order to provide a detailed future outlook, our projections have been segmented on the basis of scale of operation (preclinical, clinical and commercial), type of vector (AAV vector, adenoviral vector, lentiviral vector, retroviral vector, plasmid DNA and others), application area (gene therapy, cell therapy and vaccine), therapeutic area (oncological disorders, rare disorders, neurological disorders, sensory disorders, metabolic disorders, musco-skeletal disorders, blood disorders, immunological diseases, and others) and geographical region (North America, Europe, Asia Pacific, MENA, Latin America and rest of the world). In order to account for future uncertainties and to add robustness to our model, we have provided three forecast scenarios, namely conservative, base and optimistic scenarios, representing different tracks of the industrys growth.

The research, analysis and insights presented in this report are backed by a deep understanding of key insights generated from both secondary and primary research. For the purpose of the study, we invited over 300 stakeholders to participate in a survey to solicit their opinions on upcoming opportunities and challenges that must be considered for a more inclusive growth. The opinions and insights presented in this study were also influenced by discussions held with senior stakeholders in the industry. The report features detailed transcripts of interviews held with the following industry and non-industry players:Menzo Havenga (Chief Executive Officer and President, Batavia Biosciences)Nicole Faust (Chief Executive Officer & Chief Scientific Officer, CEVEC Pharmaceuticals)Cedric Szpirer (Former Executive & Scientific Director, Delphi Genetics)Olivier Boisteau, (Co-Founder / President, Clean Cells), Laurent Ciavatti (Former Business Development Manager, Clean Cells) and Xavier Leclerc (Head of Gene Therapy, Clean Cells)Alain Lamproye (Former President of Biopharma Business Unit, Novasep)Joost van den Berg (Former Director, Amsterdam BioTherapeutics Unit)Bakhos A Tannous (Director, MGH Viral Vector Development Facility, Massachusetts General Hospital)Eduard Ayuso, DVM, PhD (Scientific Director, Translational Vector Core, University of Nantes)Colin Lee Novick (Managing Director, CJ Partners)Semyon Rubinchik (Scientific Director, ACGT)Astrid Brammer (Senior Manager Business Development, Richter-Helm)Marco Schmeer (Project Manager, Plasmid Factory) and Tatjana Buchholz (Former Marketing Manager, Plasmid Factory)Brain M Dattilo (Business Development Manager, Waisman Biomanufacturing)Beatrice Araud (ATMP Key Account Manager, EFS-West Biotherapy)Nicolas Grandchamp (R&D Leader, GEG Tech)Graldine Gurin-Peyrou (Director of Marketing and Technical Support, Polypus Transfection)Naiara Tejados, Head of Marketing and Technology Development, VIVEBiotech)Jeffery Hung (Independent Consultant)

All actual figures have been sourced and analyzed from publicly available information forums and primary research discussions. Financial figures mentioned in this report are in USD, unless otherwise specified.

RESEARCH METHODOLOGYThe data presented in this report has been gathered via secondary and primary research. For all our projects, we conduct interviews with experts in the area (academia, industry, medical practice and other associations) to solicit their opinions on emerging trends in the market. This is primarily useful for us to draw out our own opinion on how the market may evolve across different regions and technology segments. Wherever possible, the available data has been checked for accuracy from multiple sources of information.

The secondary sources of information include:Annual reportsInvestor presentationsSEC filingsIndustry databasesNews releases from company websitesGovernment policy documentsIndustry analysts views

While the focus has been on forecasting the market over the period 2022-2035, the report also provides our independent view on various technological and non-commercial trends emerging in the industry. This opinion is solely based on our knowledge, research and understanding of the relevant market gathered from various secondary and primary sources of information.

KEY QUESTIONS ANSWEREDWho are the leading players (contract service providers and in-house manufacturers) engaged in the development of vectors and gene therapies?Which regions are the current manufacturing hubs for vectors and gene therapies?Which type of vector related technologies are presently offered / being developed by the stakeholders engaged in this domain?Which companies are likely to partner with viral and non-viral vector contract manufacturing service providers?Which partnership models are commonly adopted by stakeholders engaged in this industry?What type of expansion initiatives are being undertaken by players in this domain?What are the various emerging viral and non-viral vectors used by players for the manufacturing of genetically modified therapies?What are the strengths and threats for the stakeholders engaged in this industry?What is the current, global demand for viral and non-viral vector, and gene therapies?How is the current and future market opportunity likely to be distributed across key market segments?

CHAPTER OUTLINES

Chapter 2 is an executive summary of the insights captured in our research. It offers a high-level view on the likely evolution of the vector and gene therapy manufacturing market in the short to mid-term, and long term.

Chapter 3 is a general introduction to the various types of viral and non-viral vectors. It includes a detailed discussion on the design, manufacturing requirements, advantages, limitations and applications of the currently available gene delivery vehicles. The chapter also features the clinical and approved pipeline of genetically modified therapies. Further, it includes a review of the latest trends and innovations in the contemporary vector manufacturing market.

Chapter 4 provides a detailed overview of close to 150 companies, featuring both contract service providers and in-house manufacturers that are actively involved in the production of viral vectors and / or gene therapies utilizing viral vectors. The chapter provides details on the year of establishment, company size, location of headquarters, type of product manufactured (vector and gene therapy / cell therapy / vaccine), location of manufacturing facilities, type of manufacturer (in-house and contract services), scale of operation (preclinical, clinical and commercial), type of vector manufactured (AAV, adenoviral, lentiviral, retroviral, plasmid DNA and others) and application area (gene therapy, cell therapy, vaccine and others).

Chapter 5 provides an overview of close to 70 industry players that are actively involved in the production of plasmid DNA and other non-viral vectors and / or gene therapies utilizing non-viral vectors. The chapter provides details on the the year of establishment, company size, location of headquarters, type of product manufactured (vector and gene therapy / cell therapy / vaccine), location of plasmid DNA manufacturing facilities, type of manufacturer (in-house and contract services), scale of operation (preclinical, clinical and commercial) and application area (gene therapy, cell therapy, vaccine and others).

Chapter 6 provides an overview of close to 90 non-industry players (academia and research institutes) that are actively involved in the production of vectors (both viral and non-viral) and / or gene therapies. The chapter provides details on the year of establishment, type of manufacturer (in-house and contract services), scale of operation (preclinical, clinical and commercial), location of headquarters, type of vector manufactured (AAV, adenoviral, lentiviral, retroviral, plasmid DNA and others) and application area (gene therapy, cell therapy, vaccine and others).

Chapter 7 features an in-depth analysis of the technologies offered / developed by the companies engaged in this domain, based on the type of technology (viral vector and non-viral vector related platform), purpose of technology (vector manufacturing, gene delivery, product manufacturing, transduction / transfection, vector packaging and other), scale of operation (preclinical, clinical and commerical), type of vector involved (AAV, adenoviral, lentiviral, retroviral, non-viral and other viral vectors), application area (gene therapy, cell therapy, vaccine and others) and leading technology providers.

Chapter 8 presents a detailed competitiveness analysis of vector manufacturers across key geographical areas, featuring a four-dimensional bubble representation, taking into consideration supplier strength (based on its experience in this field), manufacturing strength (type of product manufactured, number of manufacturing facilities and number of application area), service strength (scale of operation, number of vectors manufactured and geographical reach) and company size (small, mid-sized and large).

Chapter 9 features detailed profiles of some of the key players that have the capability to manufacture viral vectors / plasmid DNA in North America. Each profile presents a brief overview of the company, its financial information (if available), details on vector manufacturing facilities, manufacturing experience and an informed future outlook.

Chapter 10 features detailed profiles of some of the key players that have the capability to manufacture viral vectors / plasmid DNA in Europe. Each profile presents a brief overview of the company, its financial information (if available), details on vector manufacturing facilities, manufacturing experience and an informed future outlook.

Chapter 11 features detailed profiles of some of the key players that have the capability to manufacture viral vectors / plasmid DNA in Asia-Pacific. Each profile presents a brief overview of the company, its financial information (if available), details on vector manufacturing facilities, manufacturing experience and an informed future outlook.

Chapter 12 features tabulated profiles of the other key players that have the capability to manufacture viral vectors / plasmid DNA. Each profile features an overview of the company, its financial performance (if available), information related to its manufacturing capabilities, and an informed future outlook.

Chapter 13 features in-depth analysis and discussion of the various partnerships inked between the players in this market, during the period, 2015-2022, covering analysis based on parameters such as year of partnership, type of partnership(manufacturing agreement, product / technology licensing, product development, merger / acquisition, research and development agreement, process development / optimization, service alliance, production asset / facility acquisition, supply agreement and others), scale of operation (preclinical, clinical and commercial) and type of vector (AAV, adenoviral, lentiviral, retroviral, plasmid and others) most active players (in terms of number of partnerships).

Chapter 14 features an elaborate discussion and analysis of the various expansions that have been undertaken, since 2015. Further, the expansion activities in this domain have been analyzed on the basis of year of expansion, type of expansion (new facility / plant establishment, facility expansion, technology installation / expansion, capacity expansion, service expansion and others), geographical location of the facility, type of vector (AAV, adenoviral, lentiviral, retroviral, plasmid and others) and application area (gene therapy, cell therapy, vaccine and others).

Chapter 15 highlights potential strategic partners (vector based therapy developers and vector purification product developers) for vector and gene therapy product manufacturers, based on several parameters, such as developer strength, product strength, type of vector, therapeutic area, pipeline strength (clinical and preclinical). The analysis aims to provide the necessary inputs to the product developers, enabling them to make the right decisions to collaborate with industry stakeholders with relatively more initiatives in the domain.

Chapter 16 provides detailed information on other viral / non-viral vectors. These include alphavirus vectors, Bifidobacterium longum vectors, Listeria monocytogenes vectors, myxoma virus based vectors, Sendai virus based vectors, self-complementary vectors (improved versions of AAV), minicircle DNA and Sleeping Beauty transposon vectors (non-viral gene delivery approach) and chimeric vectors, that are currently being utilized by pharmaceutical players to develop gene therapies, T-cell therapies and certain vaccines, as well. This chapter presents overview on all the aforementioned types of vectors, along with examples of companies that use them in their proprietary products. It also includes examples of companies that are utilizing specific technology platforms for the development / manufacturing of some of these novel vectors.

Chapter 17 presents a collection of key insights derived from the study. It includes a grid analysis, highlighting the distribution of viral vectors and plasmid DNA manufacturers on the basis of their scale of operation and type of manufacturer (fulfilling in-house requirement / contract service provider). In addition, it consists of a heat map of viral vector and plasmid DNA manufacturers based on the type of vector (AAV, adenoviral vector, lentiviral vector, retroviral vector and plasmid DNA) and type of organization (industry (small, mid-sized and large) and non-industry). The chapter also consists of six world map representations of manufacturers of viral / non-viral vectors (AAV, adenoviral, lentiviral, retroviral vectors, and plasmid DNA), depicting the most active geographies in terms of the presence of the organizations. Furthermore, we have provided a schematic world map representation to highlight the geographical locations of key vector manufacturing hubs across different continents.

Chapter 18 highlights our views on the various factors that may be taken into consideration while pricing viral vectors / plasmid DNA. It features discussions on different pricing models / approaches that manufacturers may choose to adopt to decide the prices of their proprietary products.Chapter 19 features an informed analysis of the overall installed capacity of the vectors and gene therapy manufacturers. The analysis is based on meticulously collected data (via both secondary and primary research) on reported capacities of various small, mid-sized and large companies, distributed across their respective facilities. The results of this analysis were used to establish an informed opinion on the vector production capabilities of the organizations by company size (small, mid-sized and large), scale of operation (clinical and commercial), type of vector (viral vector and plasmid DNA) and region (North America, Europe, Asia Pacific and the rest of the world).

Chapter 20 features an informed estimate of the annual demand for viral and non-viral vectors, taking into account the marketed gene-based therapies and clinical studies evaluating vector-based therapies. This section offers an opinion on the required scale of supply (in terms of vector manufacturing services) in this market. For the purpose of estimating the current clinical demand, we considered the active clinical studies of different types of vector-based therapies that have been registered till date. The data was analyzed on the basis of various parameters, such as number of annual clinical doses, trial location, and the enrolled patient population across different geographies. Further, in order to estimate the commercial demand, we considered the marketed vector-based therapies, based on various parameters, such as target patient population, dosing frequency and dose strength.

Chapter 21 presents a comprehensive market forecast analysis, highlighting the likely growth of vector and gene therapy manufacturing market till the year 2030. We have segmented the financial opportunity on the basis of type of vector (AAV vector, adenoviral vector, lentiviral vector, retroviral vector, plasmid DNA and others), application area (gene therapy, cell therapy and vaccine), therapeutic area (oncological disorders, rare disorders, neurological disorders, sensory disorders, metabolic disorders, musco-skeletal disorders, blood disorders, immunological diseases, and others), scale of operation (preclinical, clinical and commercial) and geography (North America, Europe, Asia Pacific, MENA, Latin America and rest of the world). Due to the uncertain nature of the market, we have presented three different growth tracks outlined as the conservative, base and optimistic scenarios.

Chapter 22 highlights the qualitative analysis on the five competitive forces prevalent in this domain, including threats for new entrants, bargaining power of drug developers, bargaining power of vector and gene therapy manufacturers, threats of substitute technologies and rivalry among existing competitors.

Chapter 23 provides details on the various factors associated with popular viral vectors and plasmid DNA that act as market drivers and the various challenges associated with the production process. This information has been validated by soliciting the opinions of several industry stakeholders active in this domain.

Chapter 24 presents insights from the survey conducted on over 300 stakeholders involved in the development of different types of gene therapy vectors. The participants, who were primarily Director / CXO level representatives of their respective companies, helped us develop a deeper understanding on the nature of their services and the associated commercial potential.

Chapter 25 summarizes the entire report, highlighting various facts related to contemporary market trend and the likely evolution of the viral vector, non-viral vector and gene therapy manufacturing market.

Chapter 26 is a collection of transcripts of the interviews conducted with representatives from renowned organizations that are engaged in the vector and gene therapy manufacturing domain. In this study, we spoke to Menzo Havenga (Chief Executive Officer and President, Batavia Biosciences), Nicole Faust (Chief Executive Officer & Chief Scientific Officer, CEVEC Pharmaceuticals), Cedric Szpirer (Former Executive & Scientific Director, Delphi Genetics), Olivier Boisteau, (Co-Founder / President, Clean Cells), Laurent Ciavatti (Former Business Development Manager, Clean Cells) and Xavier Leclerc (Head of Gene Therapy, Clean Cells), Alain Lamproye (Former President of Biopharma Business Unit, Novasep), Joost van den Berg (Former Director, Amsterdam BioTherapeutics Unit), Bakhos A Tannous (Director, MGH Viral Vector Development Facility, Massachusetts General Hospital), Eduard Ayuso, DVM, PhD (Scientific Director, Translational Vector Core, University of Nantes), Colin Lee Novick (Managing Director, CJ Partners), Semyon Rubinchik (Scientific Director, ACGT), Astrid Brammer (Senior Manager Business Development, Richter-Helm), Marco Schmeer (Project Manager, Plasmid Factory) and Tatjana Buchholz (Former Marketing Manager, Plasmid Factory), Brain M Dattilo (Business Development Manager, Waisman Biomanufacturing), Beatrice Araud (ATMP Key Account Manager, EFS-West Biotherapy), Nicolas Grandchamp (R&D Leader, GEG Tech), Graldine Gurin-Peyrou (Director of Marketing and Technical Support, Polypus Transfection), Naiara Tejados, Head of Marketing and Technology Development, VIVEBiotech) and Jeffery Hung (Independent Consultant)

Chapter 27 is an appendix, which provides tabulated data and numbers for all the figures in the report.

Chapter 28 is an appendix that provides the list of companies and organizations that have been mentioned in the report.Read the full report: https://www.reportlinker.com/p06323417/?utm_source=GNW

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Viral Vector Manufacturing, Non-Viral Vector Manufacturing and Gene Therapy Manufacturing Market by Scale of Operation, Type of Vector, Application...

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