The Genetics Podcast EP 226: Scaling AAV gene therapy: Engineering delivery, safety, and cost with David Dismuke of Forge Biologics and Steven Gray of UT Southwestern
Feb 12, 2026
Steven Gray, a pediatric professor engineering AAVs for CNS delivery, and David Dismuke, CTO scaling GMP AAV manufacturing, discuss translating AAV from lab to industry. They cover capsid engineering for brain delivery, manufacturing workflows and analytics, full versus empty particle impacts on safety, and how scale and platform choices could cut costs and enable next‑gen gene editing.
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Empty Capsids Affect Safety Not Just Potency
- Empty capsids increase antigen load without therapeutic benefit and can affect safety even if potency (full particles) is unchanged.
- Clinical safety events drive scrutiny back to manufacturing attributes like empty/full ratios.
Full/Empty Ratios Result From Design And Process
- Full-versus-empty ratios depend on vector design, capsid, and the manufacturing process; yields vary widely (10–50% full).
- Downstream enrichment methods (ultracentrifugation, ion exchange) trade purity for yield and throughput.
Why Gene Therapies Are So Expensive Now
- High development and manufacturing risk explain current multimillion-dollar gene therapy prices.
- As production yields and capsid efficiency improve, per-dose costs should fall dramatically over time.