Category Archives: Gene Medicine

Introduction

Laryngeal cancer is a relatively common malignant tumor in the head and neck, accounting for 15% of malignant tumors in the body. Squamous cell carcinomas account for 9698% of laryngeal cancers. Incidences of laryngeal cancer are increasing yearly as the smoking population expands, and the environment deteriorates. In 2015, there were 26,400 new cases of laryngeal cancer in China. Among these, 14,500 people died. The male to female ratio was 9:1.1 The incidence of laryngeal cancer is high in middle-aged and older males. In recent years, more incidences of laryngeal cancer are being found in the younger population, with significant differences among different races and regions.2 In China, the incidence of laryngeal cancer is highest in the Northeast and the North. In the United States, over the past 40 years, the percentage of patients with laryngeal cancer who survive for five years or more has decreased from 66% to 63%,3 suggesting the need for innovation in detection and treatment. Mitochondria are widely involved in cellular activities, including the regulation of cell cycle, oxidative stress, and apoptosis.4 Mitochondrial DNA (mtDNA) injury is closely correlated with tumors, aging, and neurodegenerative diseases.5,6 The D-loop region is the non-coding region in mtDNA. Most of the regulatory sequences related to the mtDNA replication, transcription, and translation are found in this region, which is prone to mutation. Although there have been achievements in the field concerning the relationship between tumorigenesis and mitochondrial mutation, and some related research at home and abroad have clarified some related mechanisms, the research on the relationship between tumorigenesis and mtDNA remains unclear. Moreover, no direct relationship between the abnormal changes of mtDNA and tumorigenesis has been found so far. Although many studies have reported the relationship between mitochondrial gene mutations and various tumors, the study on the mechanism of laryngeal cancer has not been reported. The purpose of the present study was to investigate the relationship between the D-loop gene mutation in mtDNA and the clinical and pathological parameters of laryngeal cancer by gene sequencing.

From June 2013 to June 2019, 60 patients with squamous cell laryngeal carcinoma were selected from the First Affiliated Hospital of Henan University of Science and Technology. No patients received radiotherapy or chemotherapy before the operation. The age ranged between 4080, with an average age of 59.12 10.35. There were 55 males and five females. There were 15 cases in stage I, 26 in stage II, ten in stage III, and nine in stage IV (according to the 2017 UICC staging criteria). The specimens from all cases were diagnosed and screened by the pathological experts of the First Affiliated Hospital of Henan University of Science and Technology. This study was approved by the medical ethics committee of the Henan University of Science and Technology. Written informed consent was obtained from all participants. This study complied with the Declaration of Helsinki.

DNA Marker DL2000 (CB15727772 TAKARA, Japan); 10Xbuffer (Mg2+plus) (DR001AM TAKARA, Japan); dNTPs (DR001AM TAKARA, Japan); Taq DNA polymerase (DR001AM TAKARA, Japan); agarose (D1200 Beijing Solabo Technology Co., Ltd); Primers (JN0060-02 Shanghai Bioengineering Technology Co., Ltd).

Thermo high-speed centrifuge (USA); PCR instrument (ABI, USA); Gel imaging system (USA); 80C refrigerator (Japan).

The specimens resected during laryngeal cancer surgery were removed, and the central part of the specimen with cancer focus was taken as the cancer tissue. Approximately 20 mg of the cancer tissue was cut and placed in a centrifuge tube. The tissue was broken into cell suspension by a high-speed tissue homogenizer. The following procedures were operated according to the kit instructions. After a series of extraction and washing, the final purified DNA solution was placed in a 20C refrigerator for storage and further detection.

The sequence in the D-loop region in mtDNA was the target sequence with a full length of 1122 bp. The primers and probes were synthesized by the Shanghai Bioengineering Technology Service Co., Ltd. The sequences of primers were as follows: the upper primer 5-CCATTAGCACCCAAAGCTAAG-3, the lower primer 5-TGCTTTGAGGTAAGCTACA-3. The reaction system was 50 L, with 5 L of the 10 buffer (Mg2+ plus) solution, 4 L of the mixture of dNTP, 0.25 L of the DNA polymerase, and 1 L of the upper primer and 1 L of the lower primer, 1 L of the template DNA, and 37.75 L of distilled water. The reaction conditions were as follows: 94C 30s, 55C 30s, 72C 90s, with a total of 30 cycles. The electrophoresis of the PCR products was under the condition of 120V for 30 minutes. After the electrophoresis, the gel imaging system was used to take photos to confirm that the amplified fragment was the desired target fragment.

The purification of the PCR products and the determination of gene sequences were completed by the Beijing Sequencing Department of Shanghai Yingjun Biotechnology Co., Ltd. The quality of the peak map was evaluated by Chromas 2.31 software, and the samples with low quality were re-sequenced. After landing on the website (https://www.Ncbi.Nlm.Nih.gov), the Align two (or more) sequences using BLAST software was used to compare the gene sequence of laryngeal cancer tissue with the Cambridge standard sequence. Once the mutation site is identified, the Chromas software should be adopted to observe the sequencing peak and compare it with the databases reported mutation site. If there is no report, it is considered a novel mutation. At the same time, these mutation sites were compared with the sub-database of the polymorphic sites of the mtDB database. If the mutation frequency was more than 1% in all populations tested in the database, it was regarded as the single nucleotide polymorphism (SNP). The gene sequencing data was provided in the Supplementary Document.

The Prism GraphPad 5.0 software was used for statistical analysis of the results. The Pearsons or the Spearman correlation test was adopted to test the correlation between the two variables, and 2 test was used to compare the number of mutations between genders. P < 0.05 was considered statistically significant.

The length of the target gene was 1122bp after the PCR amplification of the full length of the D-loop region (Figure 1). A single bright band was demonstrated by the gel imaging instrument, and the molecular weight was determined by the standard of DL2000DNAMark.

Figure 1 Results of the mtDNA PCR product.

Among the 60 samples, 38 mutation sites had been detected in 51 samples (85%), with a total of 174 mutations. In three HV in the D-loop, 160 mutations had been detected, accounting for 91.9% of the total mutations (Table 1). Microsatellite instability existed in the D310 regions in 15 cases (25%) (Figure 2), mainly manifested as the increased insertion of poly-C. Among them, nine cases showed insertion of one base C, six cases showed insertion of two bases, and the base pair exchanges within a microsatellite were found in two cases (Figure 3).

Table 1 Sequencing Results and Analysis

Figure 2 Microsatellite instability in D310 region (insertion of base pair C).

Figure 3 Microsatellite instability in D310 region (T, C exchange).

As shown in Table 2, there was no correlation between the age, gender, tumor diameter, TNM stage, and the number of the D-loop mutations in mtDNA in the 51 specimens with mutations (P > 0.05).

Table 2 The Correlation Between the D-Loop Region Mutations in mtDNA and the Clinical and Pathological Parameters in Laryngeal Cancer (Number of Cases)

Mitochondria are the only organelles with DNA outside the nucleus in the eukaryotes, which are the main sites for oxidative phosphorylation to produce active oxygen and provide necessary energy and oxygen radicals for cell activities. When mtDNA mutation occurs, the cellular energy supply is dysfunctional, and a large number of ROS are produced. This leads to changes in cell function and even cell necrosis, thus showing a variety of clinical symptoms. Mitochondrial dysfunction may play an important role in tumor development, early diagnosis, drug resistance, prevention of recurrence, and prognosis.79 MtDNA is a closed-loop double-stranded DNA molecule composed of 16,569 base pairs. As the main non-coding region, the D-loop region of npl6024-np576 is responsible for regulating mtDNA replication and transcription.10 Sanchez-Cespedes et al11 found that 41% of head and neck squamous cell carcinoma had mutations in the D-loop region, including the deletion, insertion, and point mutation. Ha et al12 revealed that patients with head and neck tumors had the change of poly-C in the D-loop region of mtDNA. Our experiment confirmed this. In recent years, the D-loop region is agreed to be the HV of mtDNA mutations. In the present study, 91.9% of the mutation sites were concentrated in the HV region, consistent with the above view. Microsatellites are the short tandem repeats in the human genome. Microsatellite instability refers to the changes of microsatellite in length and the emergence of new microsatellite alleles in tumors due to the insertion or deletion of repeat units compared with normal tissues. Habano et al13 first proposed the mitochondrial microsatellite instability in a study on rectal cancer. In the present study, microsatellite instabilities were found in 15 cases of laryngeal cancer, mainly concentrated in the D310 region and manifested as the increase of poly-C insertion. Among these cases, nine showed insertion of one base C, six showed insertion of two bases, and base exchanges within a microsatellite were found in two cases. This was consistent with the study by Sanchez-Cespedes et al that 41% of head and neck squamous cell carcinoma had mutations in the D-loop region area.11 The HV of the D310 region may be related to its location in the intron, coder, and promoter of the gene and the repeated repair caused by slip error during replication.14 Therefore, the analysis of mtDNA mutations, especially the detection of changes in the D310 region, may play an important role in the cytological diagnosis, especially for cases with no obvious morphological changes or rare tumor cells. In conclusion, PCR amplification and direct sequencing were used in the present study to detect the D-loop gene changes in mtDNA in samples of laryngeal cancer tissue. It was found that there were a large number of mutations and microsatellite instability in the D-loop region in mtDNA of patients with laryngeal cancer, indicating that the D-loop gene mutations in mtDNA may play an important role in the development of laryngeal cancer.

We would like to acknowledge the hard and dedicated work of Dr. Kai Xi and Dr. Hao Chang that helped and contributed to us in terms of technology and software of the study.

The authors report no conflicts of interest in this work.

1. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115132. doi:10.3322/caac.21338

2. Shin JY, Truong MT. Racial disparities in laryngeal cancer treatment and outcome: a population-based analysis of 24,069 patients. Laryngoscope. 2015;125(7):16671674. doi:10.1002/lary.25212

3. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):730. doi:10.3322/caac.21332

4. Correia-Melo C, Passos JF. Mitochondria: are they causal players in cellular senescence? Biochim Biophys Acta. 2015;1847(11):13731379. doi:10.1016/j.bbabio.2015.05.017

5. Bose A, Beal MF. Mitochondrial dysfunction in Parkinsons disease. J Neurochem. 2016;139(Suppl 1):216231. doi:10.1111/jnc.13731

6. Lee J, Chang JY, Kang YE, et al. Mitochondrial energy metabolism and thyroid cancers. Endocrinol Metab. 2015;30(2):117123. doi:10.3803/EnM.2015.30.2.117

7. Chen N, Wen S, Sun X, et al. Elevated mitochondrial DNA copy number in peripheral blood and tissue predict the opposite outcome of cancer: a meta-analysis. Sci Rep. 2016;18(6):37404. doi:10.1038/srep37404

8. Huang X, Zhou X, Hu Q, et al. Advances in esophageal cancer: a new perspective on pathogenesis associated with long non-coding RNAs. Cancer Lett. 2018;28(413):94101. doi:10.1016/j.canlet.2017.10.046

9. St John JC. Mitochondrial DNA copy number and replication in reprogramming and differentiation. Semin Cell Dev Biol. 2016;52:93101. doi:10.1016/j.semcdb.2016.01.028

10. Morandi L, Asioli S, Cavazza A, Pession A, Damiani S. Genetic relationship among atypical adenomatous hyperplasia, bronchioloalveolar carcinoma and adenocarcinoma of the lung. Lung Cancer. 2007;56(1):3542. doi:10.1016/j.lungcan.2006.11.022

11. Sanchez-Cespedes M, Parrella P, Nomoto S, et al. Identification of a mononucleotide repeat as a major target for mitochondrial DNA alterations in human tumors. Cancer Res. 2001;61(19):70157019.

12. Ha PK, Tong BC, Westra WH, et al. Mitochondrial C-tract alteration in premalignant lesions of the head and neck: a marker for progression and clonal proliferation. Clin Cancer Res. 2002;8(7):22602265.

13. Habano W, Sugai T, Nakamura SI, Uesugi N, Yoshida T, Sasou S. Microsatellite instability and mutation of mitochondrial and nuclear DNA in gastric carcinoma. Gastroenterology. 2000;118(5):835841. doi:10.1016/S0016-5085(00)70169-7

14. Lin CS, Lee HT, Lee MH, et al. Role of mitochondrial DNA copy number alteration in human renal cell carcinoma. Int J Mol Sci. 2016;17(6):814. doi:10.3390/ijms17060814

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Clinical Significance of the D-Loop Gene Mutation in Mitochondrial DNA | OTT - Dove Medical Press

Welcome to this week's Chutes & Ladders, our roundup of hirings, firings and retirings throughout the industry. Please send the good wordor the badfrom your shop to Fraiser Kansteiner, and we will feature it here at the end of each week.

TevardBiosciencesGopi Shanker, Ph.D., lands at the startup as chief scientific officer.

Shanker's departure marks something of a trend for Novartis. In late April,Jeff Engelman, M.D., Ph.D.,left the Novartis Institutes for Biomedical Research (NIBR) to stand up the new oncology biotechTreelineBiosciences. Just a few days later, fellow Novartis cancer R&D execPeter Hammerman, M.D., Ph.D., leftto start as chief scientific officer of molecular machines biotech MOMA Therapeutics.Shanker, for his part, will take up the post ofchief scientific officer at gene therapy startup TevardBiosciences. After heading upneuroscience atNIBR, Shanker will nowlead the preclinical scientific programs at the transfer RNA-based gene therapystartup.A few months back, Tevard forged a pact withZogenix to seek out and work on gene therapies for Dravet syndrome, a rare form of epilepsy, and other genetic epilepsies.Fierce Biotech

Blueprint MedicinesPercy Carter, Ph.D., takes up the helm of chief scientific officer.

Carter is in good company at Blueprint, where he joins former Bristol Myers Squibb compatriotFouad Namouni, M.D., who became president of R&D last fall. Carter, who joinedBristol Myers Squibb in 2001and eventually rose through the ranks tosenior vice president and head of discovery, willspearhead research and preclinical development as the new chief scientific officer at Blueprint. More recently, Carter held posts atJohnson & Johnson, where he was global head of discovery sciences in the healthcare giant's Janssen unit, andFibroGen, where he was in the CSO seat for less than a year. He joins Blueprint a little over a year after the company's first approval. In January 2020,Ayvakit,kinase inhibitor, became the first targeted treatmentfor patients with a type of stomach cancer called gastrointestinal stromal tumor who carry a (PDGFR) exon 18 mutation.Fierce Biotech

IovanceBiotherapeuticsMariaFardis, Ph.D.,is hitting the exit.

Fardis, who's also Iovance's president and a director, alertedthe company on Tuesday that she wasresigning topursue other opportunities," Iovance quietly revealed in a Wednesday securities filing. Her exit coincides withadditional data requests on potency assays for Iovance'slead candidate lifileucelfrom the FDA.Iovancewill continue validating the potency assays and expects to submit further data and meet with the FDA in the second half of 2021.The setback pushesIovancesbiologics license application submission into the first half of 2022,the company said. The "optics" of Fardis departure are "challenging" and raise "questions about whether something else is behind the change or whether the Board chose to make the change, Jefferies analysts wrote to clients this week. Long term,we think the drug works [] and it will eventually get to market," the Jefferies team added.IovancesBoard will appoint general counsel Frederick Vogt, Ph.D., as interim president and CEO. The company will immediately kick off the huntfor a successor.Fierce Biotech

>Passage Bio has bidadieu to chief medical officer Gary Romano, M.D., Ph.D. The gene therapy startup and Romanomutually agreed they should part waysTuesday, and Romano hit the exit that same day.Chief Financial Officer Richard Morris is also leaving the company on May 30, but Passage Bio described the situation differently: It said Morris' departure was not the result of any disagreement regarding any matter relating to the Companys operations, financial statements, internal controls, auditors, policies, or practices. Passage didn't say whether Romano's departure was the resultof a disagreement.Fierce Biotech

>Merck KGaA has slottedChris Round into the role ofpresident at its North America healthcare unit, replacing Andrew Patterson, who'll step into the newly minted role of chief marketing officer.EMD Serono is hoping to cash in with three promising drugsits Pfizer-partnered immuno-oncology medBavencio, multiple sclerosis treatment Mavenclad and Tepmetko for non-small cell lung cancer.Round will be based in Rockland, Massachusetts. He served for 20 years at Merck & Co. before arriving at Merck KGaA in 2017 to spearheadcommercial operations in Asia, the Middle East and Africa.Fierce Pharma

>Clinical Ink, a global clinical trial technology firm, has summoned Janette Morgan as EVP, general manager, Europe, the Middle East and Africa. Morgan joins after a 13-year run at Medidata, where she most recently served as vice president, global partner initiatives & partner business management. In that role, she was in charge ofglobal leadership and management of Medidatas Partner Study-by-Study business.Release

>Xenter, hot on the heels of last week's $12 million series A, has enlistedScott Heuler as senior vice president of global sales and marketing, whileGary Baldwin signs onas chief technology officer in Xenter'shospital technologies business unit.Baldwin previously led R&D, engineering and product teams for multiple organizations. Heuler, for his part, has held seniorsales and marketing leadership roles with NeuroOne Medical Technologies, Guidant Corporation and U.S. Surgical Corporation, Xenter said.Release

> Clinical-stage immuno-oncology companyMedicenna has tapped Mann Muhsin, M.D., as chief medical officer. With more than 20 years experience in medical practice and drug development, Muhsin signs on with "an outstanding track record of innovation in oncology and immuno-oncology trial design," Medicenna said in a release. Muhsin kicked off his clinical research career atPICR phase I unit, where he conducted more than 17 clinical trials for international sponsors likeAstraZeneca,Hoffmann La Roche, Merck, Novartis, Eli Lilly, Johnson & Johnsonand Bayer. He then went on to lead early clinical development programs at Johnson & Johnson's Janssen unit.Release

>CDMO and clinical supply services company Experic is putting David Wood in charge as chairman and chief executive officer. Over a 30-year run in the industry, Wood has lead organizations and teams atCaptek Softgel International, Catalent Pharma Solutions, Cardinal Health PTS and Becton Dickinson. He's taking the reins from Jeffrey McMullen, one of Experic's founders and its former chairman and CEO. McMullen took on aninterim CEOrole in 2019 after the untimely passing of the executive previously managing the company.Release

>NeuBase Therapeutics, looking to push its first drug candidate into the clinic next year, will welcomeSandra Rojas-Caro, M.D., as chief medical officer onMay 24. At NeuBase, she'll be in charge of thepreclinical and clinical development, medical, and regulatory strategy of NeuBases pipeline. She most recently worked at Gemini Therapeutics, where she held the same post. Before that, she was CMO atAeglea BioTherapeutics.Release

>Rain Therapeutics, working on precision oncology therapeutics, has lifted co-founderRobert Doebele, M.D., Ph.D., into the role ofpresident and chief scientific officer. Doebele co-founded Rain with chairman and CEOAvanish Vellanki in 2017. Before he joined the company full-time in October 2020, Doebele served asassociate professor of medicine in the division of medical oncology at the University of Colorado School of Medicine, director of the Thoracic Oncology Research Initiative at the University of Colorado Cancer Center and as principal investigator for the University of Colorado Lung Cancer Specialized Program of Research Excellence.Release

> Precision oncology firm Fore Biotherapeutics is building out its leadership team with the addition ofStacie Peacock Shepherd, M.D., Ph.D., as chief medical officer and Nora Brennan as chief financial officer. Shepherd will oversee clinical strategy and operational advancement of Fore's lead precision oncology program, FORE8394, and she will also helpexpand the company's clinical pipeline in the coming months. Brennan, for her part, previously served as CFO atTELA Bio, and held the same role at Xeris Pharmaceuticals before that.Release

>Cybrexa Therapeutics has summonedStephen Basso as its chief financial officer. Before joining the Cybrexa team, Basso served as senior vice president of finance atInozyme Pharma. He also served as vice president, North America commercial finance, global G&A at Alexion Pharmaceuticals, and as director, financial planning and analysis at Pfizer.Release

>Celularity, developing off-the-shelf cell therapiesderived from the postpartum human placenta, has signed onBradley Glover, Ph.D., as EVP and chief technology officer. At Celularity, Glover will oversee all aspects of the company's technical operations, includingprocess development, quality, manufacturing, supply chain, IT, facilities and engineering, and more. He joins the team from Kite Pharma, where he wore a number of executive hats in corporate development and technical operations.He rose through the ranks at Genentech and Roche before that.Release

> Early-stage allogeneic cell therapy company Appia Bio has enlisted Qi Wei, Ph.D. as senior vice president and head of technical operations. Wei is bringingsome serious cell and gene therapy know-how to the fold. He's had stints atNovartis, Gilead's Kite, Eli Lilly, TCR2 Therapeutics and Geneception.He had a hand in the development of several CAR-Ts, including Novartis' Kymriah and Kite and Gilead's Tecartus.Release

>Aerovate Therapeutics, working on meds for patients with rare cardiopulmonary disease, has handed the CEO torch toTimothy Noyes. Noyes was also elected to the company's board of directors in April. He previously served as president and chief executive ofProteon Therapeutics. He previously served aschief operating officer of Trine Pharmaceuticals and held the position of president of Genzymes renal division following its acquisition of GelTex Pharmaceuticals. Noyes started his industry run at Merck & Co.Release

> Biopharma product and portfolio strategy planner Prescient has appointed John Crowley as director of the company's intelligence and insight business, whileSugandh Sharma enters the role of senior director in the same business unit. Before joining the fold at Prescient, Crowleyled analyst teams at Decision Resources Group, covering rare diseases in neurology, immunology and hematology, as well as infectious diseases.Release

>Cognito Therapeutics, developing a new class ofdisease-modifying digital therapeutics to treat neurodegenerative disorders likeAlzheimers disease,tapped Everett Crosland as its chief commercial officer. He recently held the same role at AppliedVR, where he was in charge ofnational launch sales, marketingand payer strategy on the first breakthrough designated virtual reality therapeutic. Prior to that, he was VP of market access & reimbursement atPear Therapeutics.Release

>Umoja Biopharma, developing an integrated, in vivo immunotherapy platform, has signed onIrena Melnikova, Ph.D., as chief financial officer. She comes over from SVB Leerink, where she was a managing director in investment banking. Before that, shewas a managing director at Burrill & Company and, prior to that, director of strategy and external innovation at Sanofi.Release

>ONI has enlistedTyler Ralston, Ph.D., as its chief technology officer. In his role, Ralston willprovide leadership, strategic vision and oversee the research and development of ONI's technology. He signs on from the 4Catalyzer incubator, where he most recently served as CTO for Tesseract. Release

> Quanterix, working ondigital protein biomarker technology to enableprecision health, tappedMasoud Toloueas president of Quanterix and Diagnostics. He'll enter the role on June 9. He joins the team fromPerkinElmer, where he most recently served as senior vice president, diagnostics. He alsofounded and led Bioo Scientifics next generation sequencing business, which was acquired by PerkinElmer in 2016.Release

> Gene therapy firm AavantiBio has named Jessie Hanrahan, Ph.D., as Chief Regulatory Officer. She's the fifth senior executive to joins AavantiBio's leadership team in recent months and will be in charge ofglobal regulatory affairs for AavantiBios diversified pipeline of gene therapy programs targeting rare diseases with significant unmet medical need.Most recently, she was vice president of regulatory science at bluebird bio.Release

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Chutes & LaddersAnother Novartis exec answers the biotech call, this time for gene therapy startup Tevard - FierceBiotech

A blind man who could only perceive the faintest bit of light can now perceive fuzzy shapes, thanks to gene therapy and a pair of specially engineered goggles.

The man was diagnosed with a condition called retinitis pigmentosa 40 years ago, at the age of 18, according to a new report, published Monday (May 24) in the journal Nature Medicine. People with retinitis pigmentosa carry faulty genes that, due to many mutations, cause the light-sensitive cells in the retina at the back of the eye to break down, according to the National Eye Institute (NEI).

These genes would usually code for functional proteins in the retina, but instead fail to build those proteins, or make abnormal proteins that malfunction or produce substances that directly damage the retinal tissue. The condition affects roughly 1 in 4,000 people worldwide, according to the NEI, and can sometimes lead to complete blindness, as occurred in the 58-year-old patient in the new study, BBC News reported.

Related: 12 amazing images in medicine

In an attempt to treat the man's vision loss, scientists inserted genes that code for a light-sensing protein into a modified virus, then injected those genetically tweaked viral vectors into one of his eyes, the researchers reported. The protein, called ChrimsonR, is a engineered version of a light-sensitive protein found in unicellular algae, which allows the single-celled organism to detect and move toward sunlight, MIT Technology Review reported.

ChrimsonR belongs to a family of light-sensitive proteins called channelrhodopsins, hence the added "H" in crimson, and has been modified to react to colors within the reddish end of the color spectrum, namely amber light. By injecting genes for ChrimsonR into the retina specifically into retinal ganglion cells, a kind of nerve cell that sends visual signals to the brain the team hoped to make these cells sensitive to yellow-orange light, MIT Technology Review reported.

Here's where the special goggles came in. The goggles pick up changes in light intensity from the environment and then translate that signal into an intense, amber image that gets projected straight onto the patient's retina, with the aim of activating ChrimsonR. Months passed before a significant quantity of ChrimsonR accumulated in the man's eye and began to alter his vision, but eventually, he began to perceive patterns of light with help from the goggles, BBC News reported.

"The patient perceived, located, counted and touched" different objects using his treated eye, alone, and while wearing the goggles, the researchers wrote in the study. For instance, the patient could perceive a notebook and cups placed on a table in front of him, although when asked to count the cups he did not always give the correct number, according to MIT Technology Review.

Prior to receiving the therapy, the man could not detect any objects, with or without the goggles on, and following the injection, he could only see while wearing the goggles, since they convert all light into an amber hue, the researchers reported.

In addition to the notebook and cups, the patient reported being able to see the painted white lines at a pedestrian crossing, the BBC reported. "This patient initially was a bit frustrated because it took a long time between the injection and the time he started to see something," first author Dr. Jos-Alain Sahel, an ophthalmologist and scientist at the University of Pittsburgh and Institute of Vision in Paris, told the BBC. The patient began training with the goggles about 4.5 months after his injection and only started reporting improvements in his vision about 7 months after that, the team reported.

"But when he started to report spontaneously he was able to see the white stripes to come across the street you can imagine he was very excited. We were all excited," Sahel told the BBC.

Even now, the man's vision still remains fairly limited, in that he can only see monochromatic images and at a fairly low resolution. But "the findings provide proof-of-concept that using optogenetic therapy to partially restore vision is possible," senior author Dr. Botond Roska, founding director of the Institute of Molecular and Clinical Ophthalmology Basel at the University of Basel, told BBC News. ("Optogenetics" broadly describes the technique of using light and genetic modification to control the activity of neurons.)

Of course, although these initial results are exciting, the study is limited in that only one patient has received the treatment so far, James Bainbridge, a professor of retinal studies at the University College London who was not involved in the study, told the BBC.

Read more about the research in BBC News and MIT Technology Review.

Originally published on Live Science.

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Genes from algae helped a blind man recover some of his vision - Livescience.com

CAMBRIDGE, Mass. & FARGO, N.D.--(BUSINESS WIRE)--Moderna, Inc. (Nasdaq:MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, and Aldevron, LLC, the leading provider of high-quality plasmid DNA, mRNA and recombinant proteins necessary for vaccines, gene and cell therapy, gene editing and diagnostic applications, have announced their expanded collaboration in support of the Moderna COVID-19 Vaccine and additional programs in Modernas clinical development pipeline.

Specifically, Aldevron will supply plasmid DNA to serve as the genetic template for generating the COVID-19 mRNA vaccine and other investigational programs in Modernas pipeline.

Aldevron has been a long-standing partner of Moderna. We appreciate their collaboration and their expertise in the biologics space, said Juan Andres, Chief Technical Operations and Quality Officer of Moderna. We look forward to our ongoing work with this expanded partnership.

Aldevrons support of the Moderna pipeline spans nearly a decade, and were incredibly proud of the trust theyve placed in us commented Kevin Ballinger, Chief Executive Officer of Aldevron. Our deep experience, coupled with enhanced operational efficiencies and recent capacity expansion place us in an excellent position to support Modernas efforts especially during this critical time. We look forward to expanding our strategic partnership to serve a pipeline of important new programs in the future.

Aldevrons production of DNA continues to take place in its 70,000 sq ft GMP facility located in Fargo, North Dakota. Buildout and validation of an additional 189,000 sq ft expansion to the GMP facility on Aldevrons 14-acre Breakthrough Campus has been completed, enabling additional manufacturing capacity.

About Aldevron

Aldevron is a premier manufacturing partner in the global genetic medicine field. Founded in 1998 by Michael Chambers and John Ballantyne, the company provides critical nucleic acids and proteins used to make gene and cell therapies, DNA and RNA vaccines, and gene editing technologies. Aldevrons 600 employees support thousands of scientists who are developing revolutionary treatments for millions of people.

About Moderna

In 10 years since its inception, Moderna has transformed from a science research-stage company advancing programs in the field of messenger RNA (mRNA), to an enterprise with a diverse clinical portfolio of vaccines and therapeutics across six modalities, a broad intellectual property portfolio in areas including mRNA and lipid nanoparticle formulation, and an integrated manufacturing plant that allows for both clinical and commercial production at scale and at unprecedented speed. Moderna maintains alliances with a broad range of domestic and overseas government and commercial collaborators, which has allowed for the pursuit of both groundbreaking science and rapid scaling of manufacturing. Most recently, Modernas capabilities have come together to allow the authorized use of one of the earliest and most-effective vaccines against the COVID-19 pandemic.

Modernas mRNA platform builds on continuous advances in basic and applied mRNA science, delivery technology and manufacturing, and has allowed the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases, cardiovascular diseases and auto-immune diseases. Today, 24 development programs are underway across these therapeutic areas, with 14 programs having entered the clinic. Moderna has been named a top biopharmaceutical employer by Science for the past six years. To learn more, visit http://www.modernatx.com.

Modernas Forward Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including regarding: the supply by Aldevron of plasmid DNA for Moderna products, including the Companys COVID-19 vaccine. In some cases, forward-looking statements can be identified by terminology such as will, may, should, could, expects, intends, plans, aims, anticipates, believes, estimates, predicts, potential, continue, or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Modernas control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements. These risks, uncertainties, and other factors include, among others: the fact that there has never been a commercial product utilizing mRNA technology approved for use; the fact that the rapid response technology in use by Moderna is still being developed and implemented; the safety, tolerability and efficacy profile of the Moderna COVID-19 Vaccine observed to date may change adversely in ongoing analyses of trial data or subsequent to commercialization; despite having ongoing interactions with the FDA or other regulatory agencies, the FDA or such other regulatory agencies may not agree with Modernas regulatory approval strategies, components of our filings, such as clinical trial designs, conduct and methodologies, or the sufficiency of data submitted; Moderna may encounter delays in meeting manufacturing or supply timelines or disruptions in its distribution plans for the Moderna COVID-19 Vaccine; whether and when any biologics license applications and/or emergency use authorization applications may be filed and ultimately approved by regulatory authorities; potential adverse impacts due to the global COVID-19 pandemic such as delays in regulatory review, manufacturing and clinical trials, supply chain interruptions, adverse effects on healthcare systems and disruption of the global economy; and those other risks and uncertainties described under the heading Risk Factors in Modernas most recent Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission (SEC) and in subsequent filings made by Moderna with the SEC, which are available on the SECs website at http://www.sec.gov. Except as required by law, Moderna disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. These forward-looking statements are based on Modernas current expectations and speak only as of the date hereof.

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Moderna and Aldevron Announce Expanded Partnership for mRNA Vaccine and Therapeutic Pipeline - Business Wire

ZUG, Switzerland and CAMBRIDGE, Mass., May 25, 2021 (GLOBE NEWSWIRE) -- CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, today announced that members of its senior management team are scheduled to participate in the following virtual investor conferences in June:

Jefferies Virtual Healthcare ConferenceDate: Tuesday, June 1, 2021Time: 1:00 p.m. ET

William Blair 41st Annual Growth Stock ConferenceDate: Thursday, June 3, 2021Time: 12:20 p.m. ET

Goldman Sachs 42nd Annual Global Healthcare ConferenceDate: Tuesday, June 8, 2021Time: 3:00 p.m. ET

A live webcast of these events will be available on the "Events & Presentations" page in the Investors section of the Company's website at https://crisprtx.gcs-web.com/events. A replay of the webcasts will be archived on the Company's website for 14 days following each presentation.

About CRISPR TherapeuticsCRISPR Therapeutics is a leading gene editing company focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. CRISPR/Cas9 is a revolutionary gene editing technology that allows for precise, directed changes to genomic DNA. CRISPR Therapeutics has established a portfolio of therapeutic programs across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine and rare diseases. To accelerate and expand its efforts, CRISPR Therapeutics has established strategic collaborations with leading companies including Bayer, Vertex Pharmaceuticals and ViaCyte, Inc. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Cambridge, Massachusetts, and business offices in San Francisco, California and London, United Kingdom. For more information, please visit http://www.crisprtx.com.

CRISPR THERAPEUTICS word mark and design logo are trademarks and registered trademarks of CRISPR Therapeutics AG. All other trademarks and registered trademarks are the property of their respective owners.

Investors:Susan Kim, +1 617-307-7503susan.kim@crisprtx.com

Media:Rachel Eides, +1-617-315-4493Rachel.Eides@crisprtx.com

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CRISPR Therapeutics to Participate in Upcoming Investor - GlobeNewswire

Alliance for Regenerative Medicine, European Federation of Pharmaceutical Industries and Associations, and European Association for Bioindustries Call for Advanced Therapies to be Exempt from EU GMO Legislation

COVID-19 highlights how the EU can adapt legislation to meet urgent health needs

A permanent exemption would help to accelerate access to life-changing medicines for European patients

BRUSSELS, BELGIUM May 25, 2021

The European Commission should exempt advanced therapies from Genetically Modified Organism (GMO) legislation, which hurts Europes ability to attract clinical trials and delays patient access to transformative medicines, said the Alliance for Regenerative Medicine (ARM), the European Federation of Pharmaceutical Industries and Associations (EFPIA), and the European Association of Bioindustries (EuropaBio) in a paper published online yesterday in the journal Human Gene Therapy.

The European Commission recognized that GMO requirements hinder the conduct of clinical trials in its April 29 study on new genomic techniques and in the 2020 Pharmaceutical Strategy for Europe, when it called for GMO legislation to be fit for purpose for addressing medicines. The original GMO legislation was primarily enacted to protect food consumers and the environment, but Advanced Therapy Medicinal Products (ATMPs) such as gene therapies are affected as an unintended consequence. The uneven application of GMO requirements across EU Member States causes significant clinical trial delays despite findings that gene therapies pose a negligible risk to the environment.

Galvanized by the pandemic, the European Commission granted a temporary derogation from GMO requirements to investigational COVID-19 medicinal products to accelerate the development of vaccines and treatments. An industry survey suggested that the temporary derogation decreased the amount of time required to complete clinical trials in Europe. A similar, but permanent, exemption is justified for gene therapies -- which often treat life-threatening diseases that have few, or no, treatment options while still preserving high quality and safety standards.

The European Commission recognised that time was of the essence when lifting GMO requirements for COVID-19 vaccines and treatments, said Paige Bischoff, ARMs Senior Vice President of Global Public Affairs. Time is also very much of the essence for people with cancer, inherited disorders and other life-threatening conditions. We call on the European Commission to take the same measures for advanced therapies and remove the unnecessary and unintended burden of GMO legislation so patients have timely access to transformative, potentially curative medicines.

The organisations call on the European Commission to put forward a proposal by 2022, the timeframe proposed by the Pharmaceutical Strategy for Europe. Without an exemption for gene therapies, the GMO requirements threaten the regions competitiveness with other parts of the world where GMO legislation is less complex and cumbersome. A 2019 ARM report, for example, found that the number of ATMP clinical trials in Europe stayed roughly flat over a four-year period (2014-2018) while increasing substantially in North America (+36%) and in Asia (+28%). Europe is at risk of falling further behind: At the end of 2020 the ATMP sector was conducting 1,220 clinical trials worldwide, up from 1,066 in 2019.

"In 2020, we welcomed the derogation from GMO legislation for COVID-19 treatments or vaccines in clinical trials, said Pr Tellner,Director of Regulatory Affairs at EFPIA. Member companies are increasingly reporting how the derogation has removed the significant and time-consuming hurdles associated with GMO submissions, in addition to the clinical trial application. Swift action to a permanent exemption from GMO legislation allows the EU to prosper and most importantly for patients to continue to receive transformative, potentially life-saving therapies."

Freeing the conduct of clinical trials with investigational gene therapies from the heavy EU GMO administrative burden is critical for cutting-edge biotechnology companies, added Violeta Georgieva, EuropaBios Legal Affairs Manager. The use of CRISPR/Cas9, the latest promising tool in genome editing, can be overshadowed in the EU if developers and regulators are to follow the 2018 ruling of the EU Court of Justice, which puts the controversial GMO label on the Nobel Prize-winning CRISPR technology. Our hopes are set on the European Commission to improve patient access to revolutionary treatments by exempting them from the disproportionate and outdated GMO framework.

ARM, EFPIA, and EuropaBio look forward to engaging with the European Commission and other stakeholders to find the best possible solutions to ensure that Europe is a competitive destination for the development of advanced therapies and that European patients have access to the most innovative, life-changing treatments.

Press enquiries

For more information or for media requests, please contact Stephen Majors from the Alliance for Regenerative Medicine at smajors@alliancerm.org, Andy Powrie-Smith from EFPIA at communications@efpia.eu, or Dovile Sandaraite from EuropaBio at d.sandaraite@europabio.org.

About the Alliance for Regenerative Medicine (ARM)

The Alliance for Regenerative Medicine (ARM) is the leading international advocacy organisation dedicated to realizing the promise of advanced therapy medicinal products (ATMPs).ARMpromotes legislative, regulatory, reimbursement and manufacturing initiativesin Europe and internationally to advance this innovative and transformative sector, which includes cell therapies, gene therapies and tissue-based therapies.Early products to market have demonstrated profound, durable and potentially curative benefits that are already helping thousands of patients worldwide, many of whom have no other viable treatment options. Hundreds of additional product candidates contribute to a robust pipeline of potentially life-changing ATMPs.In its 11-year history,ARMhas become the global voice of the sector, representing the interests of 380+ members worldwide and 85+ members across 15 Europeancountries, including small and large companies, academic research institutions, major medical centres and patient groups.To learn more aboutARMor to become a member, visithttp://www.alliancerm.org.

About the European Federation of Pharmaceutical Industries and Associations (EFPIA)

The European Federation of Pharmaceutical Industries and Associations (EFPIA) represents the biopharmaceutical industry operating in Europe. Through its direct membership of 36 national associations, 39 leading pharmaceutical companies and a growing number of small and medium- sized enterprises (SMEs), EFPIAs mission is to create a collaborative environment that enables our members to innovate, discover, develop and deliver new therapies and vaccines for people across Europe, as well as contribute to the European economy

About the European Association for Bioindustries (EuropaBio)

The European Association for Bioindustries (EuropaBio) promotes an innovative and dynamic European biotechnology industry. EuropaBio and its members are committed to the socially responsible use of biotechnology to improve quality of life, to prevent, diagnose, treat and cure diseases, to improve the quality and quantity of food and feedstuffs and to move towards a biobased and zero-waste economy. EuropaBio represents corporate and associate members across sectors, plus national and regional biotechnology associations which, in turn, represent over 1800 biotech SMEs. Read more about our work at http://www.europabio.org.

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ARM, EFPIA and EuropaBio Call for Advanced Therapies to be - GlobeNewswire