AAV-FVIII (ΔSQ-F309S-X5)

AAV-FVIII (ΔSQ-F309S-X5) is an investigational adeno-associated virus (AAV) vector-based gene therapy designed for the treatment of hemophilia A. Developed by researchers at the Indiana University School of Medicine in collaboration with other academic institutions, the therapy utilizes an AAV8 vector under the control of a transthyretin promoter to deliver an engineered human B-domain-deleted factor VIII (BDD-FVIII) variant. This specific variant, ΔSQ-F309S-X5, incorporates several rational design modifications: the F309S mutation to reduce endoplasmic reticulum (ER) stress and protein aggregation, the X5 modification (replacing five amino acids with porcine residues) to enhance secretion efficiency, and the deletion of the SQ linker (ΔSQ) to eliminate proteolytic cleavage sites. In preclinical models, AAV-FVIII (ΔSQ-F309S-X5) demonstrated stable, long-term expression of factor VIII in the normal range with low variability and reduced cellular unfolded protein response (UPR) activation compared to wild-type BDD-FVIII.

Other names

AAV-FVIII (deltaSQ-F309S-X5)AAV8-FVIII (deltaSQ-F309S-X5)AAV8-FVIII (ΔSQ-F309S-X5)AAV8-deltaSQ-F309S-X5AAV-8-deltaSQ-F309S-X5AAV 8-deltaSQ-F309S-X5deltaSQ-F309S-X5deltaSQ-F-309S-X5deltaSQ-F 309S-X5ΔSQ-F309S-X5