The Vector

Volume 9, Issue 10: October 2020


Editorial Team

Edith Pfister, Ph.D. – Editor, The Vector
Karen Bulaklak, Ph.D. – Associate Editor, The Vector
Jon Brudvig, Ph.D. – Junior Editor, The Vector

Inside This Issue

Leadership Message
Breaking Through
Society News
Career Center
Public Policy
Industry News

Leadership Message


Time to Renew Your ASGCT Membership

Hello everyone,

It has been a busy and hugely successful month for ASGCT! First off, I want to let you know how pleased I was with our September programming. In a few short months, ASGCT leadership and staff were able to plan and execute the COVID-19 Symposium, where we heard from numerous medical and disease experts (including Anthony Fauci, M.D.) as well as researchers from universities and therapeutics companies who presented brand new findings. We were thrilled to host more than 2,000 virtual attendees; if you missed it, you can still register for free and watch all the content on demand for 30 days following the event. During the second annual Policy Summit the following week, we heard from policy experts, industry professionals, and patient advocates who covered regulatory, government relations, market access, and ethical issues related to gene and cell therapy. The event was extremely informative and I hope all of you who attended came away inspired and ready to bring new knowledge back to your institutions. The content from the Policy Summit is also available to view on demand for registered attendees for 30 days after the event. Thank you to everyone who joined us!

As we approach the end of the year, I want to remind you that it’s time to renew your ASGCT membership for 2021. As a member of the largest and most inclusive gene and cell therapy community, you’re contributing to a unique and multidisciplinary group. Members receive discounts to events like the Annual Meeting and the Policy Summit, a free online subscription to our field-leading journal Molecular Therapy, eligibility to apply for grants and awards, and more. I think our September programming has shown just how important our members are in advancing the field of gene and cell therapy. If you haven’t already, renew your membership now!

And last but not least, it’s already time to talk about next year’s Annual Meeting! The current plan is to hold the 24th Annual Meeting from May 12-15, 2021 in Portland, OR and to facilitate virtual access along the lines of the 2020 meeting for attendees unable or unwilling to travel. The Call for Abstracts for the 2021 meeting will open on Monday, November 16. Additionally, we are excited to welcome the 2021 plenary speakers, Michel Sadelain, M.D., Ph.D., and Robert Martuza, M.D. More information is available on the Annual Meeting website. We look forward to seeing your abstracts!

In the meantime, I hope you’re all staying healthy and well.

Stephen J. Russell, M.D., Ph.D.
ASGCT President

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Breaking Through


PTEN Inhibition Ameliorates Muscle Degeneration and Improves Muscle Function in a Mouse Model of Duchenne Muscular Dystrophy

Yue F, Song C, Huang D, Narayanan N, Qiu J, Jia Z, Yuan Z, Oprescu S, Roseguini B, Deng M, Kuang S

DOI: https://doi.org/10.1016/j.ymthe.2020.09.029

Summary by Jon Brudvig, Ph.D.

Duchenne muscular dystrophy (DMD), a severe X-linked muscular dystrophy, is caused by a deficiency in the dystrophin protein, which forms part of the link between the muscle fiber cytoskeleton and the extracellular matrix. DMD has been a challenging treatment target for gene therapies, due in part to the large size of the protein (427 kDa). While a number of research teams are working to develop therapies for DMD based on miniaturized transgenes or overexpression of the smaller utrophin homologue, potential also exists to find druggable targets that modulate muscle fiber integrity or regeneration. In a September 2020 Molecular Therapy article from Yue, et al., the authors show that phosphatase and tensin homolog (PTEN) could be one such target.

PTEN is a ubiquitously expressed tumor suppressor and growth regulator that exerts its effects by dephosphorylating PIP3 and thus regulating downstream AKT activity. Building upon earlier findings showing elevated skeletal muscle PTEN levels in DMD patients, Yue, et al. explored the impact of Pten deletion in DMD using a conditional knockout mouse model. When Pten was deleted from the MyoD+ skeletal muscle lineage in D2.B10 Dmdmdx mice, a range of myopathological, histopathological and behavioral phenotypes improved to wild type or intermediate levels at early-adult time points. Pten deletion increased muscle size, improved grip strength and running performance, and improved sarcolemma integrity. RNAseq revealed upregulation of numerous genes involved in maintenance of the extracellular matrix and basement membrane, concomitant with downregulation of genes involved in inflammation and immune responses. Importantly, the authors were able to recapitulate many of these findings with short-term pharmacological inhibition of PTEN using VO-OHpic trihydrate.

Could PTEN inhibition be a viable treatment strategy in DMD? While the Yue, et al. (2020) study shows great potential, more work will be required to bring this approach to the clinic. In tissues other than skeletal muscle, PTEN inactivation leads to the development of cysts, growths, and tumors, suggesting that a targeted approach would be necessary. As the authors suggest, recent advances in tissue-specific nanoparticle targeting could possibly facilitate this, as could targeted gene therapy strategies. Additionally, it is unclear whether PTEN inhibition provides similar benefits for cardiac muscle and other affected tissues in DMD, and whether benefits can be maintained with long-term therapy. In any case, these findings shed new light on the therapeutic potential of modulating PTEN and related cellular growth pathways in DMD, and perhaps even in other degenerative muscle disorders.

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Society News


ASGCT 24th Annual Meeting Website is Now Live

We hope you're getting excited for the 24th Annual Meeting, held May 12-15, 2021, in Portland, OR. You can now visit annualmeeting.asgct.org for the most up-to-date information about the meeting, and new information will be added as it is confirmed. The Call for Abstracts will open on Monday, November 16, 2020 and registration will open in early December.

Renew Your Membership to Maintain Your Benefits

Make sure you renew your ASGCT membership for 2021! Online renewal is quick and secure, and you won't lose access to benefits like event discounts, grant and award eligibility, and more. Renew your membership in the largest and most inclusive gene and cell therapy community today!

Register for the 2020 NORD Summit

It's not too late to register for the 2020 NORD Rare Diseases and Orphan Products Breakthrough Summit, which is happening virtually today and tomorrow. Leading experts, advocates, industry KOLs and senior staffers from FDA and NIH will be discussing critical issues including the COVID-19 pandemic’s impact on the rare disease community, telehealth, drug pricing, advancements in technology, tools for accelerating cures, and more.

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Career Center


Are you looking for a job in the field of gene and cell therapy? Check out the new ASGCT Career Center for great opportunities with industry, government, and academic organizations. Sign up to receive alerts for open jobs in your area.

If you're from a recruiting institution, advertise in the Featured Jobs section to target the 4,000+ audience of The Vector.

Featured Jobs

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Public Policy


ASGCT Policy Summit Features Luminary Speakers on Key Issues in the Field

ASGCT hosted the second annual Policy Summit September 23-25 in a virtual format. The final agenda featured speakers addressing various aspects of the opportunities and challenges of gene and cell therapy development, access, and responsible use.

Highlights included a keynote from George Q. Daley, M.D., Ph.D., Dean of the Faculty of Medicine & Caroline Shields Walker Professor of Medicine at Harvard Medical School. Daley highlighted the role of science advocacy, and called for scientists to responsibly educate, advocate, and critically analyze the work they do as new technologies like gene editing and stem cells continue to be studied. Panels on responsible use of technology and nontherapeutic uses of gene editing rounded out the ethics portion of the 2020 Policy Summit.

Turning to regulatory issues, panelists took on key issues in the field surrounding large-scale manufacturing, CMC, and other regulatory topics. Kicking off Day 2 with the Summit’s second keynote, Director of FDA CBER Peter Marks, M.D., Ph.D., noted FDA’s need for a significant increase in staff to keep up with the workload of advancing gene therapies quickly and safely. He addressed FDA’s work with the Foundation for the NIH on efforts to increase standardization of AAV vectors, vector generation processes, and regulatory requirements, to be able to treat ultrarare diseases in a precompetitive space.

Michelle McMurry-Heath, M.D., Ph.D., CEO of the Biotechnology Innovation Organization, utilized her keynote and fireside chat to discuss the urgent need of the scientific community to address treatment and coverage disparities that make it more difficult for vulnerable communities to access gene and cell therapies. A session on evidence generation for regulators and payers uniquely included discussion on data requirements for both regulatory approval and payer coverage. Patient access and payment policy were among the topics discussed in welcome remarks from U.S. Senator Tim Scott and in a session on policies related to gene therapies for sickle cell disease when they reach approval.

The final keynote from Joe Grogan, former Director of the United States Domestic Policy Council, included an emphasis on the importance of active industry involvement in the next iteration of the Prescription Drug User Fee Act (PDUFA), which will be reauthorized in 2022. He advised industry to submit fully baked proposals to FDA on issues such as attracting the best scientists as reviewers. The Summit also focused on the new topics this year of market access in the EU and newborn screening policies.

On-demand presentations are available until October 25, and you can still register here for full access! Sign in from the Policy Summit Welcome page, click on “Sessions” and type in the name and email you used to register. Once you are signed in, you will be able to view the agenda and recorded sessions.

ASGCT Elevates Attention to Gene Therapy in Bill

Last month an updated version of H.R. 4764, reauthorizing the C.W. Bill Young Cell Transplantation Program, was released that also codifies attention to regenerative medicine into the Public Health Service Act (PHSA), based on input from ASGCT. Additionally, the bill was amended to explicitly include gene therapies and genetically-modified cells in the definition of regenerative medicine, using language ASGCT helped draft and advocate for. With funding for the Regenerative Medicine Innovation Program (RMIP) ending in 2020 (created by 21st Century Cures in 2016), ASGCT is working to ensure funding for the program continues. While funding for RMIP will need to come from the appropriations process, the bill is a first step in elevating the need for specific attention to gene therapy research funding. The bill passed the House on September 30 and will go to the Senate.

Industry News


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2020

ASGCT Policy Summit

September 23-25, 2020