AAV Gene Therapy

Overview

Adeno-associated virus gene therapy delivering factor VIII or IX genes to liver cells via IV infusion; one product approved for hemophilia B achieves annualized bleeding rate of 0.4/year but faces gradual expression decline and low commercial uptake (~$90M 2025 sales) from a cautious patient community. AAV gene therapy for hemophilia delivers factor VIII or IX genes via intravenous infusion to infect liver cells, where the gene reaches the nucleus and drives expression of the deficient clotting factor; manufacturing had to scale from HEK293 adherent transient expression at very low yields to suspension culture processes with massively increased yields. Critical quality attributes for AAV products include phosphorylation, deamidation, and isomerization of the capsid, and the ratio of full to empty capsids; initial manufacturing required approximately one bioreactor per patient before process optimization via DOE and improved purification made the process commercially viable. (Gene Therapy Overview (10:00-15:00))