The Vector
Volume 11, Issue 3: March 2022
Editorial Team
Edith Pfister, PhD – Editor, The Vector
Karen Bulaklak, PhD – Associate Editor, The Vector
Jon Brudvig, 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
Send Your Late-Breaking Abstracts by March 18
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Hello ASGCT Members,
As you are likely aware, planning for the upcoming Annual Meeting is in full swing and progressing well; I hope you’re all registered for the meeting and any of our 13 Pre-Meeting Workshops. You can search the agenda to view confirmed speakers and start planning the sessions you want to attend. For the first time in ASGCT’s history, we’re accepting late-breaking abstracts, which will present data that is high impact, groundbreaking, innovative, and newsworthy. If you have late-breaking research that you’d like to present at the meeting, send it to us by March 18. If you’re an Associate Member and the first and presenting author of an accepted abstract, you can register for the meeting for free.
While you’re registering for the Annual Meeting, please make sure you renew your ASGCT membership. This will ensure you have benefits like discounts for the Annual Meeting and Insight Series, and access to the Professional Development Café archive for the rest of 2022. Please renew by Tuesday, March 15.
We have two notable events this month. Our next Professional Development Café, How to Set Up Pre-Clinical Studies, is happening today, March 11, at 1 p.m. (CT) This café is the first of a two-part series hosted by Andrew Steinsapir, a gene therapy program lead at Deerfield Discovery and Development. As always, the event will be available on demand and there will be time for Q&A from the audience.
Intro to Viral Vectors, our next Patient Education Lunch & Learn, will be held Thursday, March 31. We’ll be hearing from Stefanos Koutsoukos, Lauriel Earley, PhD, and Carmen Unzu, PhD, about how vectors are used in gene therapy, how safety is prioritized in their development, and more. Visit this blog post for upcoming dates and topics for this series, and watch past events here. The Lunch & Learn series is off to a strong start and I hope you’ll join us for one of their upcoming events.
Lastly, I’ve been really impressed with our first four Insight Series events and I encourage anyone who hasn’t attended a live session yet to watch them on demand at your convenience. These sessions provide informative, unique programming and I look forward to sharing more information with you about upcoming sessions later this year. Again – we are looking forward to seeing you all in person in D.C. this May!
Sincerely,
Beverly L. Davidson, PhD
ASGCT President
Breaking Through
A novel regulatory mechanism network mediated by lncRNA TUG1 that induces the impairment of spiral artery remodeling in preeclampsia
Xu Y, Wu D, Hui B, Shu L, Tang X, Wang C, Xie J, Yin Y, Sagnelli M, Yang N, Jiang Z, Zhang Y, Sun L
DOI: https://doi.org/10.1016/j.ymthe.2022.01.043
Summary by Edith Pfister, PhD
Preeclampsia (PE) is a hypertensive disorder of pregnancy. A leading cause of maternal and infant mortality worldwide, preeclampsia affects 2-8% of pregnancies and the only treatment is delivery of the baby. The placenta plays a critical role in the development of PE; early in pregnancy, extravillous trophoblasts invade the maternal decidua and myometrium, leading to spiral artery remodeling. The transformation of the spiral arteries into high-flow, low-resistance vessels ensures adequate blood flow to the uteroplacental bed. Impairments in this process are associated with placental defects and PE. It is thought that the impairment of placentation causes an immune response and chronic inflammation, which is triggered by abnormal levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). While sFlt-1 and PlGF are interesting targets for treatment, evidence suggests that non-coding RNAs, including miRNAs and lncRNAs may contribute to the development of PE.
In a new paper in Molecular Therapy, Xu et al. examine the role the lncRNA TUG1 in spiral artery remodeling and establish a regulatory pathway involving miR-218, FOXP1 and TUG1. In HTR-8/SVneo cells, downregulation of TUG1 using an siRNA led to an increase in TET3, DUSP2, DUSP4, and DUSP5. TUG1 interacts with the Histone-lysine N-methyl transferase SUV39H1. Downregulation of SUV39H1 also upregulates TET3, DUSP2, DUSP4 and DUSP5 and in cells treated with TUG1 siRNA, binding of SUV39H1 to its targets and H3K9me3is reduced, suggesting that TUG1 regulates its target genes by recruiting SUV39H1.
They further show that the DNA demethylase TET3 regulates the DUSP family members and that methylation of DUSP2 and DUSP4 is increased in preeclamptic, but not normal, placenta. The regulatory pathway also appears to involve the hypoxia responsive miR-218, which inhibits FOXP1. Most importantly, the authors correlate changes in components of the regulatory pathway in preeclamptic placenta. This suggests that this pathway might be an interesting and potentially useful target for intervention or diagnosis in PE.
From Molecular Therapy
Now open: Search for Molecular Therapy—Oncolytics editor-in-chief: ASGCT has opened its search for the next editorial leader of MTO as the inaugural editor-in-chief Dr. Yuman Fong’s term ends Dec. 31, 2022. MTO is an online, open-access journal focusing on the development and clinical testing of viral, cellular, and other biological therapies targeting cancer. Its 2020 impact factor is 7.200.
Applications must include a letter of intent detailing relevant experience and vision for the journal as well as a current C.V. Interested ASGCT members may submit inquiries to ASGCT CEO David Barrett.
Molecular Therapy—Methods and Clinical Development call for papers: Submit a paper to a special issue on evidence generation and reproducibility in cell and gene therapy research. Learn more about this special issue by reading this editorial and submit a paper by April 30, 2022.
March MT issues: Check out the March issues of these Molecular Therapy family journals:
Society News
Send Your Late-Breaking Abstracts by March 18
For the first time in ASGCT history, we're accepting late-breaking abstracts for presentation at the 25th Annual Meeting. If you're working on gene and cell therapy research that is high impact, groundbreaking, innovative, and newsworthy, please send us your work by March 18! The late-breaking abstract deadline is not intended to be an extension of the general submission deadline.
Free Event Today: How to Set Up Pre-Clinical Studies
Join us Friday, March 11, for our next Professional Development Café on setting up pre-clinical studies. This café is the first of a two-part series hosted by Andrew Steinsapir, a gene therapy program lead at Deerfield Discovery and Development. Register here and save the date for part two on April 8.
Broaden Your Viral Vector Knowledge on March 31
During the next free Patient Education Lunch & Learn on March 31, our experts are talking about viral vectors. We'll hear from Stefanos Koutsoukos, Lauriel Earley, PhD, and Carmen Unzu, PhD, who will dive into what vectors are, safety aspects, and more. Register here to join us.
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
Public Policy
Increased Funding for NIH, FDA Included in FY22 Omnibus Appropriations Bill
On March10 a bipartisan omnibus funding package for fiscal year (FY) 2022 passed in the Senate after the House voted it through March 9. President Biden is expected to sign the bill. The budget appropriates $45 billion for the National Institutes of Health (NIH), a $2.25 billion increase over FY21, and $3.3 billion for the Food and Drug Administration (FDA), a $102 million increase over FY21. Additionally, the bill includes $1 billion for ARPA-H.
ASGCT Weighs In on Using Registries for Regulatory Decision Making
ASGCT provided feedback to FDA on the draft guidance document Real-World Data: Assessing Registries to Support Regulatory Decision-Making for Drug and Biological Products. The guidance outlines considerations for sponsors who propose to use an existing patient data registry, or who propose creating a new one, to support FDA decision making on products including cell and gene therapies (CGT). The use of real-world evidence is especially important for products that are expected to have large treatment effects that can be demonstrated by registry data, real-world evidence (RWE), and historical external controls. CAR T-cell therapies, for example, have relied heavily on RWE to demonstrate effectiveness to FDA.
In our comments, the Society advocated for several key points, including:
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Greater alignment between FDA centers and review divisions on how RWE and registry information can be used to support gene and cell therapy product development
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That FDA continue to recognize the distinctive features of CGT compared to small molecule products, and take those differences into consideration in the final guidance
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Additional transparency about data sources the Agency already has access to outside of individual product sponsor applications
ASGCT will watch for the final guidance to be released and will continue to engage on the issue of real-world evidence utilization in CGT.
Don't Miss Policy-Focused Programming at the 25th Annual Meeting
ASGCT has a full slate of scientific and policy-focused symposia from May 16-19, available in a new, hybrid format. Check out the complete list of symposia and register to attend here.
For those with regulatory and clinical development interests, join a special town hall-style symposium to hear high-level regulators from FDA and the European Medicines Agency (EMA) discuss the current outlook for clinical development in 2022 and beyond. Peter Marks, MD, PhD, director of FDA CBER, and Ana Hidalgo-Simon, MD, PhD, head of advanced therapies at EMA, will address upcoming guidance documents, new policies, and convergence efforts between regulatory bodies. Additionally, the Effective Regulatory Interactions symposium aims to facilitate more effective FDA/sponsor communication within the rapidly expanding gene and cell therapy realm by discussing how to optimize early and late-stage communications with FDA.
The Accelerated Approvals for Gene Therapies symposium is tailored to researchers looking to learn more about the accelerated approval pathway and its relevance to CGT. The program will also consider a patient perspective on accelerated approval address the pathway’s significance in treating rare diseases.
Investigators in translational science won’t want to miss the symposium Competing with Best Available Care: Perspectives on Lowering Burden of Treatment with Cell and Gene Therapies. Speakers will discuss the issue of informed patient choice and patient access to gene and cell therapies in cases when there are treatment options available, but cell and gene therapies present favorable risk-benefit profile. This discussion will particularly focus on equity and access, safety considerations, and regulatory issues.