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