AAV Integration Roundtable

August 18, 2021 | 8 a.m.-3 p.m. (CT)

Adeno-associated virus (AAV) vectors are currently used to develop a wide range of therapies for many conditions given their ability to effectively transduce various cell types to produce long-term expression of transgenes. AAV vectors are known to deliver transgenes via in vivo gene delivery to support long-term expression. While some vectors (e.g., gammaretrovirus, lentivirus, foamy virus etc.) are known to be integrating, other vectors such as AAV, have been historically understood to result in low levels of integration. Although AAV vector genomes can persist within cells as episomes, varying reports from pre-clinical research suggest that more research is necessary to better understand the integration profile. The risk of rAAV-mediated oncogenesis in humans is theoretical, with no confirmed genotoxic events reported to date. However, there is a need to further understand and contextualize this phenomenon to inform further research, regulatory needs, and patient care.

Agenda

Co-Chairs: Kevin Eggan, Ph.D. and Douglas McCarty, Ph.D.

8:00 am – 8:05 am: Beverly Davidson, Ph.D.: Opening Remarks: ASGCT's Involvement in AAV Integration
8:05 am – 8:20 am: Kevin Eggan, Ph.D.: Introduction and Background

8:20 am –11:05 am: Reflections from Nonclinical Data

8:20 am – 10:15 am: Expert Presentations:

8:20 am – 8:40 am: Mark Kay, M.D., Ph.D.: Characterizing AAV Integration
8:40am – 9:00am: Phillip Tai, PhD, rAAV Characterization by NGS
9:00 am – 9:20 am: Randy Chandler, Ph.D.: Rodent Study Results

9:20 am – 9:35 am: Break

9:35 am – 9:55 am: Denise Sabatino, Ph.D.: Dog Study Findings
9:55 am – 10:15 am: David Lillicrap, M.D.: Dog Study Findings
10:15 am – 10:35 am: Irene Gil-Farina, Ph.D.: In Vitro Model Systems

10:35 am – 11:20 am: Roundtable Discussion:

Nonclinical Safety and Risk Assessment*

Moderator: Douglas McCarty, Ph.D.

11:20 am – 11:50 am: Lunch Break

11:50 am – 1:35 pm: Clinical Considerations: Best Practices for Risk Assessment

11:50 am – 12:50 pm: Expert Presentations:

11:50 am – 12:10 pm: Eugenio Montini, Ph.D.: Approaches and Reflections Based on Past Experiences (e.g., adenovirus, retrovirus, etc.)
12:10 pm – 12:30 pm: Ricardo Dolmetsch, Ph.D.: uniQure Approach to Assessing Recent Data
12:30 pm – 12:50 pm: Markus Grompe, M.D.: Ensuring and Supporting Informed Decision-Making by Clinicians and Patients

12:50-1:35 pm: Roundtable Discussion:

Clinical Considerations: Best Practices for Risk Assessment*

Moderator: Kevin Eggan, Ph.D.

1:35 pm—1:50 pm: Break

1:50 pm – 4:00 pm: Roundtable Discussion on Best Practices and Post-Approval Considerations for AAV Integration Risk and Safety Assessment and to Align on Next Steps: *

Moderators: Douglas McCarty, Ph.D. and Kevin Eggan, Ph.D.

*Roundtable Expert Participants:

Fred Bushman, Ph.D.
Randy Chandler, Ph.D.
Ronald Crystal, M.D.
Ricardo Dolmetsch, Ph.D.
Guangping Gao, Ph.D.
Irene Gil-Farina, Ph.D.
Markus Grompe, M.D.
Mark Kay, MD, Ph.D.
David Lillicrap, M.D.
Eugenio Montini, Ph.D.
Denise Sabatino, Ph.D.
Dinah Sah, Ph.D.
Jing Yuan, Ph.D.