Category Archives: Gene Medicine

Studies in non-human primates demonstrated nearly 100% gene editing and knockout of endogenous RHO gene and more than 30% replacement protein levels using a dual vector AAV approach

Treated eyes showed morphological and functional photoreceptor preservation

EDIT-103 advancing towards IND-enabling studies

CAMBRIDGE, Mass., Oct. 13, 2022 (GLOBE NEWSWIRE) -- Editas Medicine, Inc. (Nasdaq: EDIT), a leading genome editing company, today announced ex vivo and in vivo preclinical data supporting its experimental medicine EDIT-103 for the treatment of rhodopsin-associated autosomal dominant retinitis pigmentosa (RHO-adRP). The Company reported these data in an oral presentation today at the European Society of Gene and Cell Therapy 29th Annual Meeting in Edinburgh, Scotland, UK.

EDIT-103 is a mutation-independent CRISPR/Cas9-based, dual AAV5 vectors knockout and replace (KO&R) therapy to treat RHO-adRP. This approach has the potential to treat any of over 150 dominant gain-of-function rhodopsin mutations that cause RHO-adRP with a one-time subretinal administration.

These promising preclinical data demonstrate the potential of EDIT-103 to efficiently remove the defective RHO gene responsible for RHO-adRP while replacing it with an RHO gene capable of producing sufficient levels of RHO to preserve photoreceptor structure and functions. The program is progressing towards the clinic, said Mark S. Shearman, Ph.D., Executive Vice President and Chief Scientific Officer, Editas Medicine. EDIT-103 uses a dual AAV gene editing approach, and also provides initial proof of concept for the treatment of other autosomal dominant disease indications where a gain of negative function needs to be corrected.

Key findings include:

Full details of the Editas Medicine presentations can be accessed in the Posters & Presentations section on the Companys website.

About EDIT-103EDIT-103 is a CRISPR/Cas9-based experimental medicine in preclinical development for the treatment of rhodopsin-associated autosomal dominant retinitis pigmentosa (RHO-adRP), a progressive form of retinal degeneration. EDIT-103 is administered via subretinal injection and uses two adeno-associated virus (AAV) vectors to knockout and replace mutations in the rhodopsin gene to preserve photoreceptor function. This approach can potentially address more than 150 gene mutations that cause RHO-adRP.

AboutEditas MedicineAs a leading genome editing company, Editas Medicine is focused on translating the power and potential of the CRISPR/Cas9 and CRISPR/Cas12a genome editing systems into a robust pipeline of treatments for people living with serious diseases around the world. Editas Medicine aims to discover, develop, manufacture, and commercialize transformative, durable, precision genomic medicines for a broad class of diseases. Editas Medicine is the exclusive licensee of Harvard and Broad Institutes Cas9 patent estates and Broad Institutes Cas12a patent estate for human medicines. For the latest information and scientific presentations, please visit http://www.editasmedicine.com.

Forward-Looking StatementsThis press release contains forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "target," "should," "would," and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. The Company may not actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including: uncertainties inherent in the initiation and completion of preclinical studies and clinical trials and clinical development of the Companys product candidates; availability and timing of results from preclinical studies and clinical trials; whether interim results from a clinical trial will be predictive of the final results of the trial or the results of future trials; expectations for regulatory approvals to conduct trials or to market products and availability of funding sufficient for the Companys foreseeable and unforeseeable operating expenses and capital expenditure requirements. These and other risks are described in greater detail under the caption Risk Factors included in the Companys most recent Annual Report on Form 10-K, which is on file with theSecurities and Exchange Commission, as updated by the Companys subsequent filings with theSecurities and Exchange Commission, and in other filings that the Company may make with theSecurities and Exchange Commissionin the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and the Company expressly disclaims any obligation to update any forward-looking statements, whether because of new information, future events or otherwise.

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Editas Medicine Presents Preclinical Data on EDIT-103 for Rhodopsin-associated Autosomal Dominant Retinitis Pigmentosa at the European Society of Gene...

Until recently, researchers could not see gene expression in an individual cell. Thanks to single cell sequencing techniques, they now can. But the timing of changes is still hard to visualize, as measuring the cell destroys it.

To address this, we developed an approach based on models in basic physics, explained Welch, treating the cells like they are masses moving through space and we are trying to estimate their velocity.

The model, dubbed MultiVelo, predicts the direction and speed of the molecular changes the cells are undergoing.

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Our model can tell us which things are changing firstepigenome or gene expression--and how long it takes for the first to ramp up the second, said Welch.

They were able to verify the method using four types of stem cells from the brain, blood and skin, and identified two ways in which the epigenome and transcriptome can be out of sync. The technique provides an additional, and critical, layer of insight to so called cellular atlases, which are being developed using single cell sequencing to visualize the various cell types and gene expression in different body systems.

By understanding the timing, Welch noted, researchers are closer to steering the development of stem cells for use as therapeutics.

One of the big problems in the field is the artificially differentiated cells created in the lab never quite make it to full replicas of their real-life counterparts, said Welch. I think the biggest potential for this model is better understanding what are the epigenetic barriers to fully converting the cells into whatever target you want them to be.

Additional authors on this paper include Chen Li, Maria C. Virgilio, and Kathleen L. Collins.

Paper cited: Single-cell multi-omic velocity infers dynamic and decoupled gene regulation, Nature Biotechnology. DOI: 10.1038/s41587-022-01476-y

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Mathematical model could bring us closer to effective stem cell therapies - Michigan Medicine

For decades, medical cancer treatment has generally meant chemotherapy, radiation, or surgery, alone or in combination. But things are changing rapidly. Today, new approaches such as immunotherapies and targeted therapies are becoming available, with many more in research and development. In many cases, the new treatments are more effective, with fewer side effects.

Its an exciting time to be in cancer research and cancer discovery, said Colin Duckett, PhD, professor of pathology, interim chair of the Department of Pharmacology and Cancer Biology, and vice dean for basic science."

Were moving into this era where we have a new set of tools we can use to treat cancer.-Colin Duckett, PhD

Researchers in the Duke Cancer Institute (DCI) and across the School of Medicine are helping to create these new tools, fueled by the knowledge and experience of experts from a wide range of disciplines.

Indeed, cancer research has always been a team-based endeavor at DCI.

DCI was specifically created a decade ago to break down barriers between disciplines to stimulate collaborative research and multidisciplinary interaction, said DCI Executive Director Michael Kastan, MD, PhD, the William and Jane Shingleton Distinguished Professor of Pharmacology and Cancer Biology.

Adding fuel to the fire is the Duke Science and Technology (DST) initiative, which aims to catalyze and support collaborative research in service of solving some of the worlds most pressing problems, including cancer.

The new tools, though varied, all represent advances in personalized cancer medicine. Targeted treatments are chosen based on the genetic signature of a patients tumor. Some immunotherapies take personalization even further, by manipulating a patients own immune cells to create a treatment for that individual alone.

To match treatments to patients, the multidisciplinary Duke Molecular Tumor Board, led by John Strickler, MD, HS11, and Matthew McKinney, MD06, HS06-09, HS10-13, helps providers identify best practices, newly approved treatments, or clinical trials for advanced cancer patients based on genetic sequencing of their tumors.

In precision cancer medicine the right therapy for the right patient at the right time all these things come together, the targeted therapies, the immunotherapy, even standard chemotherapy, all of that is part of precision cancer medicine.-Michael Kastan, MD, PhD

Immunotherapy aims to harness the power of the immune system to fight cancer. That can mean activating the immune system, energizing exhausted immune cells, or helping immune cells find cancer cells by guiding them there or by removing cancers good guy disguises.

Dukes Center for Cancer Immunotherapy supports these efforts by identifying promising basic science discoveries and building teams to translate those ideas into treatments.

"There are so many world-class basic research scientists here making discoveries..."-Scott Antonia, MD, PhD

...discoveries that are potentially translatable as immunotherapeutic strategies, said Scott Antonia, MD, PhD, professor of medicine and the centers founding director. Thats what motivated me to come to Duke, because of the great opportunity to interact with basic scientists to develop new immunotherapeutics and get them into the clinic.

Antonia believes immunotherapy has the potential to revolutionize cancer treatment, but more work remains to be done to realize its promise. The proof of principle is there, he said, but still only a relatively small fraction of people enjoy long-term survival. If we can hone immunotherapeutic approaches, thats our best opportunity.

Among the most exciting immunotherapy work being facilitated by the center involves removing a patients own T cells (a type of lymphocyte), manipulating them in the lab to make them more effective against tumors, then injecting them back into the patient.

T cells can be manipulated in the lab in a number of different ways. In one approach, called CAR T-cell therapy, the T cells are engineered with an addition of synthetic antibody fragments that bind to the patients tumor, effectively directing the T cells directly to the tumor cells.

In another approach, called tumor-infiltrating lymphocyte (TIL) adoptive cell therapy, the subset of a patients T cells that have already managed to find their way into the tumor are extracted and then grown to large numbers before being returned to the patient. Antonia and his colleagues recently published a paper demonstrating the effectiveness of TIL expansion in lung cancer. Were now doing the preparative work to develop clinical trials using this approach in brain tumors, and our intention is to expand into many other cancers as well, he said.

Antonia points out that innovations in CAR T-cell therapy and TIL therapy happening at Duke are possible because of collaborations with scientists in an array of disciplines, including antibody experts like Barton Haynes, MD, HS73-75, the Frederic M. Hanes Professor of Medicine, and Wilton Williams, PhD, associate professor of medicine and surgery, at the Duke Human Vaccine Institute, and biomedical engineers like Charles Gersbach, PhD, the John W. Strohbehn Distinguished Professor of Biomedical Engineering at the Pratt School of Engineering.

Furthermore, clinical trials for these kinds of cellular therapies require special facilities to engineer or expand the cells, which are provided by Dukes Marcus Center for Cellular Cures, led by Joanne Kurtzberg, MD, the Jerome S. Harris Distinguished Professor of Pediatrics, and Beth Shaz, MD, MBA, professor of pathology. Its been a very productive collaboration highlighting how Duke is uniquely positioned to develop immunotherapeutic strategies, Antonia said.

Targeted therapies exploit a tumors weak spot: a genetic mutation, for example. The benefit is that the treatment kills only cancer cells and not healthy cells. The prerequisite is knowing the genetics and biology of the specific tumor, no simple task.

Trudy Oliver, PhD05, who joined the Department of Pharmacology and Cancer Biology faculty as a Duke Science and Technology Scholar, studies cancer development and the biology of tumor subtypes, particularly squamous cell lung cancer and small cell lung cancer.

Even within small cell lung cancer, there are subsets that behave differently from each other, she said. Some of the treatments shes identified are in clinical trials

Our work suggests that when you tailor therapy to those subsets, you can make a difference in outcome.-Trudy Oliver, PhD'05

Some of the treatments shes identified are in clinical trials.

Sandeep Dave, MD, Wellcome Distinguished Professor of Medicine, is leading an ambitious project to analyze the genomics of the more than 100 different types of blood cancer. His project will streamline the diagnosis of blood cancer and uncover potential therapy targets.

All cancers arise from genetic alterations that allow cancer to survive and thrive at the expense of the host, he said. These genetic alterations are a double-edged sword they allow these cancer cells to grow, but on the other hand they do confer specific vulnerabilities that we can potentially exploit.

Dave said his background in computer science, genetics, and oncology helped him as he designed the project, which uses huge datasets.

Weve done the heavy lifting in terms of tool development and methodology, which is ripe to be applied to every other type of cancer."-Sandeep Dave, MD

Cancer disparities are caused by a complex interplay of elements, including access to health care and other resources, institutional barriers, structural racism, and biology, such as ancestry-related genetics. For example, some genetic biological factors and social elements contribute to disparities in many types of cancer.

Cancer treatment is approaching this personalized space where patients are no longer treated with a one-size-fits-all paradigm."-Tammara Watts, MD, PhD

"Its becoming increasingly apparent that there are differences in outcome with respect to race and ethnicity, said Tammara Watts, MD, PhD, associate professor of head and neck surgery & communication sciences, and associate director of equity, diversity, and inclusion at DCI. The very broad hypothesis is that there are genetic ancestry-related changes that may play a critical role in the disparate clinical outcomes we see every day in our cancer patients.

For example, self-identified white patients with throat cancer associated with the human papilloma virus (HPV) have better outcomes compared to self-identified Black patients, even when controlling for elements such as health care access, education, and socioeconomic status.

Watts is collaborating with bioinformatics experts at DCI to try to identify significant differences in gene expression among the two groups.

Im trying to tease out differences that may be impactful for disadvantaged patients based on race and ethnicity, she said. But there could be differences that emerge that could be useful for designing targeted treatments for a broad group of patients.

Thats because a targeted treatment for a particular genetic expression that might occur more commonly in Black people would help all patients with that expression, regardless of race or ethnicity.

Watts is far from alone in doing cancer disparity research at DCI. Tomi Akinyemiju, PhD, associate professor in population health sciences, uses epidemiology to study both biological factors and social elements that contribute to disparities in many types of cancer.

Jennifer Freedman, PhD, associate professor of medicine, Daniel George, MD92, professor of medicine, and Steven Patierno, PhD, professor of medicine and deputy director of DCI, are studying the molecular basis for why prostate, breast, and lung cancer tend to be more aggressive and lethal in patients who self-identify as Black. Patierno, who has been a national leader in cancer disparities research for more than 20 years, leads the Duke Cancer Disparities SPORE (Specialized Program of Research Excellence), funded by the National Cancer Institute. The SPORE grant supports these researchers as well as other DCI teams working on cancers of the breast, lung, stomach, and head and neck.

One of the things that impresses me is that [cancer disparities research] is a high priority within DCI, said Watts, who joined the faculty in 2019. These groups are actively engaged and collaborating and asking the questions that will drive change for patients who have worse outcomes that are related to ancestry.

Even better than a cancer cure is avoiding cancer altogether.

At DCI, Meira Epplein, PhD, associate professor in population health sciences, and Katherine Garman, MD02, MHS02, HS02-06, HS09, associate professor of medicine, are looking to decrease the incidence of stomach cancer by improving detection and treatment of the bacteria Helicobacter pylori, which can set off a cascade leading to stomach cancer. Epplein and Garman, also funded by the Duke Cancer Disparities SPORE grant, hope their work will reduce disparities because H. pylori infections and stomach cancer are both more prevalent among African Americans than whites.

When preventing cancer isnt successful, the next best thing is to detect and treat early. A relatively new concept in cancer care is interception, which means catching cancer just as, or even just before, it begins.

The point is to prevent it from progressing to full blown malignancy, said Patierno. In other words, stop the cancer from getting over its own goal line.

Patierno envisions a future where patients with pre-cancerous conditions or early cancer could take a pill to halt cancer development without killing cells in other words, a non-cytotoxic treatment, unlike standard chemotherapy.

We know its there, but were not going to poison it or burn it or cut it out because all of those have side effects. Were going to find a non-cytotoxic way to prevent it from progressing. Thats the goal.-Steven Patierno, PhD

Read About Alumni Making a Differencein Cancer Research and Care:

Changing theStatus Quo: Lori Pierce MD'85

Treatingthe WholePerson:Arif Kamal, MD,HS12, MHS15

Targetingthe Seeds ofCancer Growth:Eugenie S. Kleinerman, MD75, HS75

A DiscoveryThat Comes Outof Nowhere:Bill Kaelin, BS79, MD82

Story originally published in DukeMed Alumni News, Fall 2022.

Read more from DukeMed Alumni News

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Developing New Tools to Fight Cancer - Duke University School of Medicine

BEIJING & BURLINGTON, Mass.--(BUSINESS WIRE)--CANbridge Pharmaceuticals Inc. (HKEX:1228), a leading global biopharmaceutical company, with a foundation in China, committed to the research, development and commercialization of transformative rare disease and rare oncology therapies, announced that data from its gene therapy research agreement with the Horae Gene Therapy Center, at the UMass Chan Medical School, was presented at the 29th European Society of Gene and Cell Therapy Annual Congress in Edinburgh, Scotland, today.

In an oral presentation, Guangping Gao, Ph.D., Co-Director, Li Weibo Institute for Rare Diseases Research, Director, the Horae Gene Therapy Center and Viral Vector Core, Professor of Microbiology and Physiological Systems and Penelope Booth Rockwell Professor in Biomedical Research at UMass Chan Medical School, discussed the study that was led by the investigator Jun Xie, Ph.D., and his team from Dr. Gaos lab, and titled Endogenous human SMN1 promoter-driven gene replacement improves the efficacy and safety of AAV9-mediated gene therapy for spinal muscular atrophy (SMA) in mice.

The study showed that a novel second-generation self-complementary AAV9 gene therapy, expressing a codon-optimized human SMN1 gene. under the control of its endogenous promoter, (scAAV9-SMN1p-co-hSMN1), demonstrated superior safety, potency, and efficacy across several endpoints in an SMA mouse model, when compared to the benchmark vector, scAAV9-CMVen/CB-hSMN1, which is similar to the vector used in the gene therapy approved by the US Food and Drug Administration for the treatment of SMA. The benchmark vector expresses a human SMN1 transgene under a cytomegalovirus enhancer/chicken -actin promoter for ubiquitous expression in all cell types, whereas the second-generation vector utilizes the endogenous SMN1 promoter to control gene expression in different tissues. Compared to the benchmark vector, the second-generation vector resulted in a longer lifespan, better restoration of muscle function, and more complete neuromuscular junction innervation, without the liver toxicity seen with the benchmark vector.

This, the first data to be presented from the gene therapy research collaboration between CANbridge and the Gao Lab at the Horae Gene Therapy Center, was also presented at the American Society for Cellular and Gene Therapy (ASGCT) Annual Meeting in May 2022. Dr. Gao is a former ASCGT president.

Oral Presentation: Poster #: 0R57

Category: AAV next generation vectors

Presentation Date and Time: Thursday, October 13, 5:00 PM BST

Authors: Qing Xie, Hong Ma, Xiupeng Chen, Yunxiang Zhu, Yijie Ma, Leila Jalinous, Qin Su, Phillip Tai, Guangping Gao, Jun Xie

Abstracts are available on the ESGCT website: https://www.esgctcongress.com/

About the Horae Gene Therapy Center at UMass Chan Medical School

The faculty of the Horae Gene Therapy Center is dedicated to developing therapeutic approaches for rare inherited disease for which there is no cure. We utilize state of the art technologies to either genetically modulate mutated genes that produce disease-causing proteins or introduce a healthy copy of a gene if the mutation results in a non-functional protein. The Horae Gene Therapy Center faculty is interdisciplinary, including members from the departments of Pediatrics, Microbiology & Physiological Systems, Biochemistry & Molecular Pharmacology, Neurology, Medicine and Ophthalmology. Physicians and PhDs work together to address the medical needs of rare diseases, such as alpha 1-antitrypsin deficiency, Canavan disease, Tay-Sachs and Sandhoff diseases, retinitis pigmentosa, cystic fibrosis, amyotrophic lateral sclerosis, TNNT1 nemaline myopathy, Rett syndrome, NGLY1 deficiency, Pitt-Hopkins syndrome, maple syrup urine disease, sialidosis, GM3 synthase deficiency, Huntington disease, and others. More common diseases such as cardiac arrhythmia and hypercholesterolemia are also being investigated. The hope is to treat a wide spectrum of diseases by various gene therapeutic approaches. Additionally, the University of Massachusetts Chan Medical School conducts clinical trials on site and some of these trials are conducted by the investigators at The Horae Gene Therapy Center.

About CANbridge Pharmaceuticals Inc.

CANbridge Pharmaceuticals Inc. (HKEX:1228) is a global biopharmaceutical company, with a foundation in China, committed to the research, development and commercialization of transformative therapies for rare disease and rare oncology. CANbridge has a differentiated drug portfolio, with three approved drugs and a pipeline of 11 assets, targeting prevalent rare disease and rare oncology indications that have unmet needs and significant market potential. These include Hunter syndrome and other lysosomal storage disorders, complement-mediated disorders, hemophilia A, metabolic disorders, rare cholestatic liver diseases and neuromuscular diseases, as well as glioblastoma multiforme. CANbridge is also building next-generation gene therapy development capability through a combination of collaboration with world-leading researchers and biotech companies and internal capacity. CANbridges global partners include Apogenix, GC Pharma, Mirum, Wuxi Biologics, Privus, the UMass Chan Medical School and LogicBio.

For more on CANbridge Pharmaceuticals Inc., please go to: http://www.canbridgepharma.com.

Forward-Looking Statements

The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, after the data on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development.

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CANbridge-UMass Chan Medical School Gene Therapy Research in Oral Presentation at the European Society of Gene and Cell Therapy (ESGCT) 29th Annual...

The poster and oral presentation winners of the Wayne State University School of Medicines ninth annual Vision Research Workshop have been announced.

The workshop, held Oct. 12, was presented by the Department of Ophthalmology, Visual and Anatomical Sciences, and the Kresge Eye Institute.

Presentation winners included:

Poster Presentations

First place: Nicholas Pryde, Assessment of NanodropperTM eyedropper attachment

Second place: Bing Ross, Mechanism of Preferential Calcification in Hydrophilic Versus Hydrophobic Acrylic Intraocular Lens

Third place: Pratima Suvas, Expression, Localization, and Characterization of CXCR4 and its ligand CXCL12 in herpes simplex virus-1 infected corneas

Oral Presentations

First place: Ashley Kramer, A comparative analysis of gene and protein expression in a zebrafish model of chronic photoreceptor degeneration

Second place: Jeremy Bohl, Long-distance cholinergic signaling contributes to direction selectivity in the mouse retina

Third place: Zain Hussain, Diagnostic and Treatment Patterns of Age-Related Macular Degeneration among Asian Medicare Beneficiaries

Mark Juzych, M.D., chair of the Department of Ophthalmology, Visual and Anatomical Sciences, and director of the Kresge Eye Institute, gave welcome remarks.Linda Hazlett, Ph.D., vice dean of Research and Graduate Programs and vice chair of the department, provided an overview of research.

The keynote speaker giving the annual Robert N. Frank, M.D., Clinical Translational Lecture, was Reza Dana, M.D., M.P.H., the Claes H. Dohlman Chair and vice chair for Academic Programs in Ophthalmology at Harvard Medical School, who presented New Ways of Doing Old Things: Translational Investigations in Management of Common Corneal and Ocular Surface Disorders.

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Winners of ninth annual Vision Research Workshop named - Wayne State University

Study characteristics

Sixteen studies were included in the analysis [46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61]. Most were quantitative (n=12), using questionnaires to assess public perceptions [46,47,48,49,50,51,52, 54, 56, 57, 59, 61]. Three studies conducted focus groups [53, 55, 60] while one study used both focus groups and a survey [58]. The US has contributed the most to this field thus far, undertaking six of the 16 studies identified in the literature search [49, 50, 52, 53, 55, 58]. This is followed by Canada (n=2) [48, 51] and Japan (n=2) [54, 59]. Each of the following countries contributed one study: Jordan [56], Korea [57], The Netherlands [61], Singapore [60], Qatar [46] and the UK [47]. Ten of the studies attempted to recruit a representative sample [46,47,48,49, 51, 53, 54, 56, 59, 61]. Higher educated participant populations (compared to the general population) were noted in four studies [48, 59,60,61]. Three studies recruited participants from specific sites [52, 55, 57]. No studies attempted to discern the views of underrepresented populations aside Mallow et al. [58] who conducted focus groups with a rural community (Table3, Supplementary File3).

Education level influenced decisions to hypothetically partake in genomic testing in different ways [49, 51, 56, 59, 61]. Three studies found that more educated individuals were more likely to be interested in testing [49, 56, 59], while two other studies found that being more educated led to more critical attitudes towards testing [51, 61]. One study found no association between education level and attitude towards testing [57]. Khadir, Al-Qerem and Jarrar [56] found that having a low perceived knowledge of genomic testings social consequences reduced the likelihood of having a reserved attitude. Abdul Rahim et al. [46] found genetic/genomic knowledge did not impact whether a participant would engage in testing.

The age of the participant was reported to influence decision making [49, 54, 56, 57, 59], with no consensus on attitudes of older versus younger adults. Lee et al. [57] found that older adults were more likely to approve of integrating personalised medicine testing into standard healthcare. Two other studies also found that older adults were slightly more interested in genomic testing [54, 56]. In contrast, Okita et al. [59] found that older adults were less willing to partake in genomic testing, while Dodson et al. [49] found no association between age and likeliness to have testing.

Abdul Rahim et al. [46] found that marital status was not significantly associated with willingness to partake in testing in Qatari adults, while Dodson et al. [49] found American participants planning to have children in the next five years had significantly increased interest in testing. Dodson et al. [49] was the only study to investigate whether ethnicity influenced decision-making, showing no association.

Okita et al. [59] assessed the influence of employment status on willingness to partake, reporting that students had significantly more positive attitudes towards testing compared to employed respondents. Bombard et al. [48] found that having an income of more than CAD$80,000 led to a 11-12% decrease in likeliness of believing parents have a responsibility to have their child tested via expanded NBS. No study assessed the impact of sex on attitude towards testing, however Lee et al. [57] found that sex did not significantly influence whether the participant had heard of personalised medicine.

Using the NASSS domains we were able to map primary source data to technology (Domain 2), value proposition (Domain 3), the adopter system (Domain 4) and the wider context (Domain 6) (Fig.2). Greenhalgh et al. [39] does not provide specific definitions for their domains, rather they frame these domains in the form of questions that need to be answered. We replicated this approach and adapted the questions to align with our study questions (Supplementary File4).

The NASSS Framework considers the influences on adoption, nonadoption, abandonment, spread, scale-up, and sustainability of healthcare technologies. Domains 2 (Technology), 3 (Value proposition), 4 (Adopter system) and 6 (Wider context) of the NASSS Framework have been addressed in this scoping review to consider how public perceptions are incorporated in the framework.

Domain 2 considers the technical aspects of the technology that will influence its implementation [39]. Questions 2B, types of data generated; 2C, knowledge needed to use the technology; and 2E, Who owns the IP generated by the technology?, are addressed in the primary sources.

This question considers the knowledge generated by the technology and how this is perceived by patients and/or caregivers. Two studies cited the accuracy of genetic information as an issue for their participants [54, 58].

Greenhalgh et al. [39] defines this as the type of knowledge needed by both healthcare providers and patients to use the technology. However, we will only focus on the views of the general public. Although patients of genomic testing do not necessarily need knowledge to undertake testing, the informed consent process is essential. To gain informed consent from patients, understanding the baseline genomic knowledge of the public is beneficial for those taking consent. Knowledge of genetics and genomics was assessed in several different ways across the included articles [46, 52,53,54, 56, 58, 60]. These included asking participants if they had heard of various genetic and/or genomic terms, how they had heard about genomic testing, how participants describe genomics (in a focus group setting) and questions on genetics knowledge.

Abdul Rahim et al. [46] found that less than a third (n=245) of survey respondents had heard of genomic testing while just over half (n=447) had heard of genetic testing. Gibson, Hohmeier and Smith [52] found that 54% (n=7) of their participants had heard the term pharmacogenomics. Hishiyama, Minari and Suganuma [54] found that more than two-thirds of their participants had heard of classic genetic terminology (e.g. DNA, gene, chromosome), whereas fewer participants had heard of newer, genomics terminology (e.g. personal genome and pharmacogenomics). Hahn et al. [53] found that the majority of their participants had not heard the term genomic medicine and personalised medicine. Ong et al. [60] found that English and Mandarin-speaking participants had heard of the term personalised medicine but not precision medicine, while Malay-speaking participants had not heard of either term.

Three studies questioned participants on how they had heard about genomics [46, 52, 53]. Abdul Rahim et al. [46] asked about both genetic and genomic testing whereas Gibson, Hohmeier and Smith [52] asked their participants where they had heard certain terms from. Abdul Rahim et al. [46] found that 30% (n=69) of participants who knew of genomic testing, heard about it through word of mouth. Gibson, Hohmeier and Smith [52] found that 54% (n=7) of participants had heard of pharmacogenomic testing, and other key terms associated with genomics, from the internet. Hahn et al. [53] used focus groups to discern participant understanding of the term genomic medicine, and found that some college students had heard of the term on the news and in biology classes.

Two studies used focus groups to discern genomic understanding [53, 58]. Mallow et al. [58] used a Community Participating Research approach. Community leaders suggested they use terms like genes and family health history rather than scientific terminology to assist discussions with the community. They found that participants were more likely to describe inheriting disease rather than inheriting health and wellness [58]. Hahn et al. [53] found that their focus group participants described genomic medicine in terms of genetics, family history, the genome project, using genetics to heal people and cloning. Ong et al. [60] also used focus groups to discuss baseline understanding of personalised medicine and precision medicine divided into the primary language spoken by the participants, allowing for discussions on terminology specific to the language.

Knowledge of genetic and/or genomic facts was directly assessed in two studies [46, 56]. Abdul Rahim et al. [46] and Khadir, Al-Qerem and Jarrar [56] both questioned respondents on their basic genetic literacy via survey questions. Abdul Rahim et al. [46] found that 56.1% of survey respondents (n=464) were able to answer at least 5 out of 8 genetic literacy questions correctly, while Khadir, Al-Qerem and Jarrar [56] found that participants were knowledgeable in hereditary genetic information but not other scientific facts. Khadir, Al-Qerem and Jarrar [56] also gave participants the opportunity to self-report their knowledge of genetics. Many participants reported having sufficient knowledge on basic medical uses of testing and potential social consequences, such as refusing testing and the rights of third parties to request genetic test results of individuals [56].

For genomic testing, we have interpreted this question to mean whether patients own their genetic information or if it belongs to the group that conducts sequencing. Four studies found that participants had concerns about the privacy of their or their childs genetic information [46, 53, 55, 57]. Hishiyama, Minari and Suganuma [54] also found that 37.1% (n=1112) of their participants were concerned about management and storage of genetic information.

Greenhalgh et al. [39] use this domain to consider the value placed on the technology by healthcare professionals and the patient. Question 3B, demand-side value (to patient), is addressed in the primary sources.

Greenhalgh et al. [39] define this question as the downstream value of the technology, including the evidence of benefit to patients and affordability. Willingness to pay for genomic testing was directly assessed in three studies [50, 52, 57]. Gibson, Hohmeier and Smith [52] found that if the entire cost of the pharmacogenomic test was covered by insurance, 89% of participants (n=24) would undertake testing [52]. Lee et al. [57] determined that age, gender, income, inconvenience of testing and prior knowledge all influenced whether participants would pay extra for personalised medical testing. Cost of testing was a concern for 44.8% of participants (n=316) [57]. Edgar et al. [50] found that most adoptees (72.4%) and non-adoptees (80.3%) were willing to pay between US$1 and US$499. Education level was a predictor for adoptee willingness to pay, while income predicted willingness to pay in non-adoptees [50]. Abdul Rahim et al. [46] did not directly assess willingness to pay, however they noted that a high income was associated with participant willingness to partake in testing.

Hahn et al. [53] and Ong et al. [60] did not directly assess willingness to pay for genomic sequencing, but participants did express concerns about the cost of testing to the individual and whether there would be equitable access to testing.

Greenhalgh et al. [39] use this domain to consider the adoption of the technology. The adopter system includes caregivers, healthcare professionals and patients. Question 4B addresses whether patients will adopt a technology, while 4C addresses if lay caregivers are available to facilitate adoption. As we did not include patients or lay caregivers in our review, we have adapted these definitions to incorporate hypothetical patients and/or carers under the term genomic naive public. Greenhalgh et al. [39] also emphasise patient acceptance and family conflict as influencing factors on use of technology.

Several personal values were identified across the included studies [46, 48,49,50,51,52,53,54, 56, 59]. Abdul Rahim et al. [46] and Hishiyama, Minari and Suganuma [54] found that contributing to science and medical research were reasons to partake [46, 54]. Other reasons for partaking in genomic testing suggested by Qatari adults included improved health knowledge and prevention of future health conditions [46]. This was also suggested by participants in Etchegary et al. [51], Hahn et al. [53] Khadir, Al-Qerem and Jarrar [56].

Bombard et al. [48] found that most of their participants preferred using scientific evidence (82%, n=994) and receiving expert advice (74%, n=897) when making important healthcare decisions. However, only half (53%) of participants had trust in healthcare (n=639). Hahn et al. [53] also found that many participants were sceptical of genomic medicine specifically, and often associated it with genetic engineering and cloning despite these not being directly related to genomic testing. Some participants felt they did not need the information genomic testing could provide, while others who would hypothetically want testing, believed it could promote the development of new treatments and provide more information on family history [53].

Primary reasons for not willing to partake in testing, as noted by Abdul Rahim et al. [46] were lack of time, information or knowledge, and privacy concerns. Similar concerns were suggested by Hahn et al. [53] and Lee et al. [57]. Fear of the unknown was also suggested in Hahn et al. [53] and Mallow et al. [58]. Participants in Hahn et al. [53] also noted they may be uncomfortable with the results, and the results may be too deterministic.

Aside from general concerns about the nature of genomic testing, concern regarding communication of genetic information among family members was also highlighted [47, 51, 53, 56, 58, 61]. Ballard et al. [47] noted that most participants, whether asked to imagine either they or a family member had a genetic condition, believed other family members who might also be affected should be notified. Etchegary et al. [51] and Khadir, Al-Qerem and Jarrar [56] also found that most participants would share genomic test results with family members. Participants in Hahn et al. [53] generally had a positive view of learning about genetic information if it would help other family members as some had family members who had passed away without explanation. Mallow et al. [58], however, found that communicating genetic information to family members may be an issue. Participants cited several reasons for this including: upsetting children and the creation of family issues, older family members not willing to disclose information and stigmatisation by the community, particularly if the information in question regarded mental illness or substance abuse disorders [58]. Participants also suggested they would only discuss genetic risk if there was a health crisis in the family [58]. Etchegary et al. [51], although noting that many participants would want to share information, found that those with the highest education levels and income were less likely to share results with family members. Vermeulen et al. [61] also found that 17% of their participants (n=160) were worried about causing friction within their families. However, participants who believed family history assessments were worthwhile cited disease prevention as a benefit to involving family members [61].

Greenhalgh et al. [39] describe the wider context as the institutional and sociocultural contexts. Examples of the wider context include health policy, fiscal policy, statements and positions of professional and peak bodies, as well as law and regulation. Here, in order to respond to our research questions, we focus on the socio-cultural aspects of the public.

Societal concerns were noted in many studies [51, 53,54,55,56, 58, 60, 61]. Twenty-two percent of participants (n=1425) in the Hishiyama, Minari and Suganuma [54] study noted employment and insurance discrimination as a concern. This was also noted in Etchegary et al. [51] and Khadir, Al-Qerem and Jarrar [56]. Participants in Hahn et al. [53] and Mallow et al. [58] noted discrimination and segregation as key societal issues that may arise. One-third of participants (n=311) in Vermeulen et al. [61] thought that individuals may be coerced into testing if it is normalised.

Cultural context may influence participant responses. For example, Abdul-Rahim et al. found the 45.1% of their respondents (n=241) were in consanguineous relationships [46]. No other study reported on consanguinity, demonstrating that different cultures prioritise different elements when reporting. Abdul-Rahim et al. found that 70.9% population (n=584) were willing to undergo genomic testing [46], whereas Dodson et al. found that 39.5% of their US population (n=805) were somewhat interested and 19.1% (n=389) were definitely interested in genomic testing [49]. These papers demonstrates that different cultures can influence perceptions of genomic testing. However, the Caucasian US population in Gibson et al. were more willing to undergo testing at 81.0% (n=21) [52], showing that even within the same country there can be cultural differences that may lead to differences in perception.

Read more here:
How does the genomic naive public perceive whole genomic testing for health purposes? A scoping review | European Journal of Human Genetics -...