This week on The Genetics Podcast, Patrick is joined by Dr. David Dismuke, Chief Technical Officer at Forge Biologics, and Dr. Steven Gray, Professor at UT Southwestern Medical Center. They discuss the evolution of AAV gene therapy from academic labs to industrial-scale manufacturing, how vector design and capsid engineering are improving CNS delivery, and what manufacturing innovation and next-generation delivery technologies mean for safety, cost, and the future of gene therapy.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to David and Steven
01:47 David and Steven’s overlapping academic paths and long-term collaboration
03:39 Steven’s research on AAV engineering for central nervous system (CNS) gene therapy
04:50 Forge Biologics’ platform approach to scalable AAV manufacturing
06:28 How AAV vectors are manufactured
08:24 How CNS AAV vectors are designed, tested, and refined across programs
10:58 How manufacturing quality and trial outcomes can shape AAV development decisions
15:13 Factors that impact the ratio of full versus empty AAV capsids
17:21 Manufacturing scale, capsid efficiency, and the future cost curve of AAV gene therapy
24:19 Scaling AAV manufacturing for common diseases and the shift toward industrialized production models
27:07 Engineered AAV capsids for CNS delivery and the tradeoffs between innovation and platform stability
30:31 Next-generation AAV delivery and gene editing technologies
34:41 Lessons from Jude Samulski on translating AAV science into real-world therapies
37:21 Closing remarks
Find out more: Forge Biologics
