The Vector
Volume 10, Issue 9: September 2021
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
From Molecular Therapy
Society News
Career Center
Public Policy
Industry News
Leadership Message
The Countdown to the Policy Summit is On
Hello ASGCT Members,
We’re less than two weeks away from the ASGCT Policy Summit! If you haven’t registered yet, secure your spot to attend in person at the JW Marriott Washington, D.C. or virtually. If you’re attending in person, you can review our safety policies here. I’m looking forward to hearing all of the great discussions on important topics in gene therapy and how they inform regulatory, legislative, and payment policies for diagnosis and treatment.
Next week, ASGCT members can join us for a free virtual symposium we’re cohosting with the International Society for Stem Cell Research (ISSCR). The program, Emerging Therapies at the Intersection of Genetic and Cellular Technologies, will be held Sept. 13-15 in three focused two-hour sessions on neural disorders, cell & gene therapy manufacturing technologies, and hematopoietic diseases and immuno-oncology. To receive free registration, visit this section of our website to get the promo code.
Also next week on Sept. 17 is our next Professional Development Café--Finding Employment in Industry from Academia. This Development Café’s goals are to help prepare for and execute an interview and how to succeed in your new role. You can register to attend this free event here. Please remember that ASGCT members can watch all past Professional Development Cafés on demand as well.
Registration is also open for the International Oncolytic Virus Conference on Nov. 5-7 in person in Sedona, AZ and virtually. This meeting brings clinical, academic, and commercial communities together to share insights and expertise for translational development of improved oncolytic viruses.
Finally, our new Annual Meeting website is up and running. Sneak a peek at the new look, and keep checking back as new meeting information will be posted as meeting events are confirmed. Also, it’s never too early to start thinking about abstract submission, which opens November 15.
Sincerely,
Beverly L. Davidson, PhD
ASGCT President
Breaking Through
AAV Integration in Human Hepatocytes
Dalwadi DA, Calabria A, Tiyaboonchai A, Posey J, Naugler WE, Montini E, Grompe M
DOI: https://doi.org/10.1016/j.ymthe.2021.08.031
Summary by Edith Pfister, PhD
On the heels of ASGCTs AAV Integration Roundtable comes a paper by Dalwadi et al. examining AAV integration in human hepatocytes. AAV has emerged as a key vector for gene therapy because of its ability to transduce a wide variety of cells and to remain mostly episomal. Low rates of genomic integration have been previously reported but have only recently gained attention as a potential safety concern. To directly examine the rate of integration in human hepatocytes, Dalwadi et al. used a humanized liver mouse model and long read PACBIO sequencing. They argue that their method overcomes some of the biases of previous methods, which rely on the presence of specific AAV sequences in the integration and do not capture the full complexity of integrants.
To humanize the mouse liver, human hepatocytes are transplanted into immune-deficient, fumarylacetoacetate hydrolase (Fah) deficient (FGRN) mice. As the human hepatocytes have a growth advantage, they quickly repopulate the liver, the accompanying cell turnover eliminates episomal rAAV. Hepatocytes were infected with rAAV by infection ex vivo or by I.V. injection of rAAV in vivo and then serially transplanted into FGRN mice. To analyze the frequency of integration, tdTomato positive cells are sorted by FACS. It is notable then that this method relies on integration of a complete and functional tdTomato transgene. Using this method, the authors found a surprisingly high (1-3%) integration rate. Integration sites were scattered across the whole genome, with a tendency to integrate within gene bodies or at transcription start sites. No full length, intact rAAV sequences were found among the integrants, but rearrangements and recombinations were frequent.
While the AAV integration showed that there is still debate about the extent to which other methods underestimate integration events, this paper clearly contributes to our understanding of rAAV integration by indicating that the rate may be higher than previously thought. In addition, the detailed examination of integrated sequences provides interesting detail. Further discussion is sure to be ongoing.
From Molecular Therapy
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Molecular Therapy call for papers: Submit your paper to a special issue dedicated to the topic of emerging diseases and the technologies being developed to address them.Learn more about the issue here and submit by October 1.
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 February 28, 2022.
Check out the latest issue of Molecular Therapy here, and don't miss these upcoming issues:
Society News
25th Annual Meeting Site is Live
You can now visit annualmeeting.asgct.org for the most up-to-date information about the 25th Annual Meeting, which will be a hybrid event May 16-19, 2022 in Washington, D.C. and virtually. Make sure you're prepared to submit your abstracts starting Nov. 15 by reading the abstract section of the website! More information will be added as it's confirmed.
Comirnaty Becomes First-Ever mRNA Vaccine to Receive FDA Approval
Last month the Pfizer-BioNTech vaccine for COVID-19, now known as Comirnaty, became the first-ever mRNA vaccine or therapeutic to receive approval from FDA, as explained by ASGCT President Beverly Davidson, PhD, in a recent blog post. To learn more about how mRNA vaccines work, visit our Patient Education site. ASGCT encourages you to share this information with your family, friends, and others in your network since protection against the virus can be built if enough people are vaccinated.
Patient Education Releases Resources on Gaucher Disease
New resources on Gaucher disease are now available on ASGCT's Patient Education site. Gaucher disease is a rare genetic disorder that causes the harmful buildup of glycolipids throughout the body because of a mutation in the GBA gene. Check out our latest video and infographic to learn how gene therapy may address symptoms caused by Gaucher's effect the disease has on the brain.
Upcoming Events and Deadlines
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
Register Now for the Third Annual ASGCT Policy Summit
In-person registration for the 2021 Policy Summit is limited and ends on Sept. 16, so register soon to secure your spot! This hybrid event will be held September 22-24 virtually and in person at the JW Marriott Washington, D.C. The Policy Summit will feature sessions on the following topics and more:
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New developments in gene and cell therapy technology
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Policies related to accelerated approval
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Issues in regulatory policy
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Prioritizing patients in therapeutic development
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Workforce development challenges
See the full agenda on our website. ASGCT has instated a number of safety policies, including physical distancing and a universal indoor mask requirement for in-person attendees; read about all our safety plans here.
ASGCT Hosts AAV Integration Roundtable
Last month ASGST held a roundtable on AAV integration, which addressed preclinical research on the integration profile of AAV vectors, considerations for clinical risk assessment, and areas in need of further research. Watch the entire event on demand. To hear a summary of insights from the roundtable you can register to attend the Policy Summit, which features a session dedicated to the topic. At the Policy Summit you will also learn how the FDA's thinking on this topic is evolving and some of the risk/benefit considerations from the perspective of hepatologist Graham Foster, PhD.
Industry News
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