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This research aims to enhance the efficacy of gene therapy vectors for hemophilia B by optimizing the factor IX transgene and capsid modifications.

December 8, 2025Blood

An engineered AAVrh10 vector containing an optimized factor IX transgene improves therapeutic response during hemophilia b gene therapy

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Engineered gene therapy significantly improves factor IX levels in hemophilia B mice, suggesting enhanced treatment efficacy.

This research aims to enhance the efficacy of gene therapy vectors for hemophilia B by optimizing the factor IX transgene and capsid modifications.
Generated AAVrh10 capsid mutants through site-directed mutagenesis and identified PTM sites via in-silico analysis.
Injected hemophilia B mice with various AAVrh10 vectors and assessed FIX levels using ELISA and clotting-based assays.
Conducted immune profiling using immunohistochemistry and Bethesda assay to evaluate potential immune responses.
AAVrh10K169Q mutants achieved the highest factor IX activity (83.8%, 7.9-fold increase) compared to wild-type vectors.
No FIX inhibitors were detected, indicating a low risk of immune activation in treated mice.
Engineered FIX transgenes sustained supraphysiological factor IX activity, ranging from 529% to 1435% from 4 to 34 weeks post-gene therapy.

Sarangi et al. (2025) studied this question.

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