October 2023
Editorial Team
Jon Brudvig, PhD – Editor, The Vector
Jessica Schneller, PhD – Associate Editor, The Vector
Wan Du, MD, PhD – Junior Editor, The Vector
Inside This Issue
Leadership Message
Breaking Through
From Molecular Therapy
Society News
Career Center
Public Policy
Industry News
Leadership Message
Take Five Minutes to Renew, Maintain Extensive Benefits Through 2024
Hello ASGCT members,
I hope you’re enjoying the beginning of fall. We’re now officially in renewal season at ASGCT and I’d encourage all of you to take a few minutes to renew your membership today. Whether you’re new to our CGT community (welcome!) or you’ve been here for a while (thank you!) there’s a lot happening in the Society these days. We put together this blog post summarizing key member benefits you can maintain through 2024 when you renew.
I’ve already renewed my membership, and it took less than five minutes. As you will note in the blog post, the benefits to membership are extensive. My favorites are the many discounts, including those for the Annual Meeting as well as access to and publishing in the Molecular Therapy family of journals.The membership directory is also extremely helpful for making contacts and seeking collaborators and assistance.Membership numbers are very helpful to the Society for future planning of the Annual Meeting and our larger scope of activities.
To make the renewal process even easier in the future, check out the auto-renew feature so you can “set it and forget it.” Thank you for your continued support of ASGCT; we could not fulfill our mission without you and we are so grateful to help you advance the field.
Monday, Oct. 16, is the beginning of ASGCT Insights Week! If you haven’t already, register for one or more expert-led sessions on back-to-back days. Focus on past Annual Meeting abstract highlights, AAV and lentiviral vectors, gene editing technology, prenatal gene and cell therapy, or innate immune responses and non-viral gene delivery. Members will save on registration and have on-demand access following the live airing, so make sure your membership is current!
Finally, I was incredibly excited to hear last week’s news that two of our colleagues, Drew Weissman, MD, PhD; and Katalin Karikó, PhD; became co-recipients of the 2023 Nobel Prize in Physiology or Medicine! Drs. Weissman and Karikó will be awarded for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19. Join me in congratulating Drs. Weissman and Karikó! Those of you who were at the 2022 Annual Meeting were treated to an incredibly interesting lecture by Dr. Weissman in what was likely a preview of his acceptance speech in Stockholm. Perhaps next year's Annual Meeting will give us a preview of the next Nobel Prize winner who has contributed to the rapid development of cell and gene therapies.
Have a great rest of the month and get ready to submit your abstracts for the 2024 Annual Meeting in November!
Sincerely,
Jeffrey Chamberlain, PhD
ASGCT President
Breaking Through
Development of an mRNA-lipid nanoparticle vaccine against Lyme disease
Pine M, Arora G, Hart TM, Bettini E, Gaudette BT, Muramatsu H, Tombácz I, Kambayashi T, Tam YK, Brisson D, Allman D, Locci M, Weissman D, Fikrig E, Pardi N
DOI: https://doi.org/10.1016/j.ymthe.2023.07.022
Summary by Wan Du, MD, PhD
Lyme disease is the most prevalent vector-borne disease, primarily caused by different species and strains of the Borrelia burgdorferi sensu lato bacteria transmitted to humans via tick bites. The symptoms of Lyme disease include fever, fatigue, headache, and a skin rash. Without proper treatment, the infection can spread to the joints, heart, and nervous system. While most Lyme disease cases respond well to a few weeks of antibiotics, a subset of individuals may experience post-treatment Lyme disease syndrome (PTLDS), characterized by persistent symptoms like severe joint pain and neurocognitive problems. What's even more concerning is that being infected with one strain doesn't provide immunity against different strains. Therefore, the development of a comprehensive preventive vaccine is essential to stop both new and recurrent cases of Lyme disease. B. burgdorferi produces a variety of proteins that could potentially serve as vaccination targets. One of these proteins is outer surface protein A (OspA), which is a surface lipoprotein abundantly present and responsible for attaching the bacterium to the tick midgut. It gets rapidly reduced during the feeding process, highlighting the importance of early targeting. In the United States, there are numerous distinct strains of B. burgdorferi that can infect humans, making OspA an attractive vaccine target due to its widespread conservation among these strains.
Back in 1998, LYMErix™, an alum-adjuvanted recombinant OspA (rOspA) protein vaccine, was released, demonstrating a 75% reduction in Lyme disease cases within a year. However, the vaccine was withdrawn from the market in 2002. Since then, there has been no Lyme disease vaccine approved by the FDA, despite a continuing increase in cases. In a recent study in Molecular Therapy, Matthew Pine et al. propose using an innovative strategy, mRNA-based lipid nanoparticle (mRNA-LNP) vaccine platform to develop a Lyme disease vaccine. The success of mRNA-LNP has extended to humans, as it prompts potent antibody and cellular immune reactions against SARS-CoV-2 virus.
The authors have designed and produced an mRNA-LNP vaccine encoding OspA and then assessed its immune response and protective effectiveness in comparison to an OspA protein subunit vaccine with alum adjuvant. The results indicated that mice received a single OspA mRNA-LNP dose exhibited stronger polyfunctional CD8+ and CD4+ T-cell responses compared to those vaccinated with the OspA protein. While the primary defense against B. burgdorferi infection in the host is through antibody responses, the presence of anti-OspA CD8+ T cells could offer additional immune reinforcement, particularly since some patients have spirochetes expressing OspA during late-stage infection. One specific subgroup of CD4+ T cells known as Tfh cells, as well as antigen-specific GCB cells were significantly greater increase in a single vaccination with OspA mRNA-LNP than with rOspA + alum. The enhanced magnitude of germinal center responses was associated with higher levels of their terminal outputs, including antigen-specific memory B cells (MBCs) and long-lived plasma cells (LLPCs). These cells secreted IgG1, IgG2a, and IgG2b antibodies following a single OspA mRNA-LNP immunization. Furthermore, with these potent immune responses, a single administration of OspA mRNA-LNP proved to be more successfully in protecting mice from B. burgdorferi infection compared to the recombinant protein counterpart.
Through further preclinical and clinical advancements, OspA mRNA-LNP may prove to be a feasible preventive strategy for reducing the prevalence of Lyme disease. Their findings also highlight the potential for developing highly effective mRNA vaccines against non-viral pathogens.
From Molecular Therapy
Read the position description here and submit your CV and cover letter by Jan. 31, 2024.
Active Calls for Papers
RNA and epigenetic editing: A new generation of precision therapeutics
Novel therapeutic targets and biomarker development
Latest MT issues: Check out the most recent issues of these Molecular Therapy family journals:
Society News
Congrats to Nobel Prize Winners Drew Weissman & Katalin Karikó
Drew Weissman, MD, PhD, and Katalin Karikó, PhD, will co-receive the 2023 Nobel Prize in Physiology or Medicine for their landmark work on mRNA technology that led to the development of the COVID-19 vaccines. Earlier this year, Dr. Weissman shared his personal journey and ups and downs of pioneering these vaccines on ASGCT’s podcast Giants of Gene Therapy.
Next Week Will be Packed With CGT Insights
ASGCT Insights Week is next week and we hope you're registered! Join us for five, two-hour sessions in five days, Oct. 16-20. Each day's speaker panel will focus on a unique topic, inlcuding top Annual Meeting abstracts, lentiviral and AAV vectors, gene editing, prenatal CGT, and innate immune responses. Get ready for a packed week of ASGCT Insights!
Watch the Policy Summit On Demand Through Oct. 23
Watch sessions on demand featuring FDA's Nicole Verdun, MD, ARPA-H's Renee Wegrzyn, PhD, and many more from the government, regulatory, and advocacy side of the field! You can re-watch your favorite Policy Summit sessions or catch anything you missed on the virtual meeting platform through Oct. 23.
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 6,000+ audience of The Vector.
Featured Jobs
Public Policy
Catch Up with FDA, CMMI, and ARPA-H On Demand Now
ASGCT works tirelessly to advocate for policies that support the work of our members and the field. This year’s Policy Summit welcomed nearly 300 in-person and virtual attendees to address the most important policy topics for the cell and gene therapy (CGT) field.
Policy Summit presenters discussed the pipeline of CGT approvals and associated challenges, highlighting the ways in which regulatory and legislative policy can help advance the field. The Summit featured several high-level fireside chats, kicking off with Dr. Nicole Verdun, new Director of the Office of Therapeutic Products (OTP), focused on overcoming staffing and workload challenges to better accommodate the incoming CGT product applications. Dr. Verdun also emphasized ways to keep reviewers up to speed on this rapidly evolving field. Dr. Renee Wegryzn, Director of the Advanced Research Projects Agency for Health (ARPA-H), outlined ways her agency is working to fund high risk, high reward projects in the CGT space that might not be viable through other avenues. Meanwhile Laura McWright, Director of the Seamless Care Models Group at the Center for Medicare & Medicaid Innovation (CMMI), unpacked the demonstration models announced by her Center earlier this year, specifically the model looking at standardizing value-based payments for CGTs. Other sessions tackled issues from patient-centered development, coverage and reimbursement, manufacturing challenges, the importance of public-private partnerships, and more.
All sessions at the Policy Summit were recorded and are available on the virtual platform. Registration and access to all the on-demand content are open through Oct. 23.
The 411 on Congress’ Government Shutdown 180
With just hours left before the end of the fiscal year on Sept. 30, both the House and Senate agreed upon and passed an unexpected Continuing Resolution (H.R.5860) to fund the government for an additional 45 days. Continuing Resolutions (CR), including this one, often include policy riders which may direct specific funding and implementation, or set priorities for the coming year. This CR provides $16 billion in emergency disaster relief and temporarily extended several programs, including Federal Aviation Administration authorities, the national flood insurance program, and various health programs.
Each fiscal year,Congress is charged with passing 12 appropriation bills to determine the allocation of funds to various government agencies, including those crucial to the advancement of cell and gene therapy like NIH and FDA. Both chambers are supposed to pass their own versions of the funding package, which then needs to be negotiated and reconciled. The bill or bills are then signed into law by the President ahead of Sept. 30, when the fiscal year ends and funding must be renewed. Frequently (including last year) most appropriations bills do not pass separately. Instead, they are packaged together in what is called an “omnibus” bill. It’s yet to be seen if Congress will pursue such a strategy this year.
It is becoming increasingly common that Congress needs additional time to create and agree on their funding plan past Sept. 30. In these cases, a short-term funding package must be passed; in the absence of either a new budget or a CR, a government shutdown occurs. This September saw intense discussions around overall federal funding levels, support for Ukraine, and other domestic issues which delayed the appropriations process. The sense in Washington, D.C. was that a government shutdown of some duration was extremely likely, and federal agencies began publishing plans for programs that would have to be paused.
With the CR passed, each chamber will now continue work on their appropriations bills before the next deadline on Nov. 17. Turmoil over the Speaker of the House of Representatives injects another level of uncertainty into the budget timeline and process. Once that contest is resolved, there are still significant differences between House and Senate budgeting priorities which will need to be reconciled. Notably, the Labor-HHS bills (which include funding for NIH) and the Agriculture-FDA bills have steeper funding cuts on the House side than in the Senate version. These differences will need to be resolved before the 2024 fiscal year budget can be set. It’s quite possible a shutdown could occur at the next deadline or thereafter.
ASGCT Returns to the Hill to Discuss the Future of Sickle Cell Disease
ASGCT recently co-hosted a briefing on Sickle Cell Disease (SCD) with Congressmen Michael Burgess, MD (TX-26) and Danny Davis (IL-07). This event brought together researchers, physicians, patient advocates, and industry developers to discuss different perspectives on the current treatment landscape for SCD – and the role CGTs will play in the future. The Society is committed to educating lawmakers on the innovative potential and practical hurdles of CGTs, and appreciates the speakers for a productive conversation:
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David Barrett, JD, CEO, ASGCT
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Stefano Rivella, PhD, Research Faculty Member, Division of Hematology, Children’s Hospital of Philadelphia
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Andrew Campbell, MD, Director, Comprehensive Sickle Cell Disease Program, Children's National Hospital
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Nasir Mason, SCD warrior and advocate
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Scott McGoohan, JD, Executive Director, Policy and Alliance Development, Vertex Pharmaceuticals
Join a Standardization Workshop at USP Headquarters
Join a free hybrid workshop Nov. 16-17 to learn about the current global status of gene therapy, gene modification, and T-cell therapy with a specific emphasis on current standardization and collaborative efforts, as well as the current challenges and gaps. The workshop will be held at the USP headquarters in Rockville, MD, and talks will also be available virtually.
Industry News
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