High-potency MyoAAV capsids enhanced skeletal muscle correction in a mouse model of GSD IIIa.

ABSTRACT: Glycogen storage disease type IIIa (GSD IIIa) affects multiple tissues, including liver, heart, and skeletal muscles. We recently reported that an adeno-associated virus serotype 9 vector expressing pullulanase, a bacterial glycogen debranching enzyme, driven by an immunotolerizing dual promoter (AAV9-Dual-Pull), effectively decreased pullulanase-induced cytotoxic T lymphocyte response and corrected disease abnormalities in all major affected tissues in GSD IIIa mice. To reduce effective vector dosages for transgene delivery to skeletal muscles, we packaged the AAV-Dual-Pull vector into two muscle-tropic MyoAAV capsids, MyoAAV4A and MyoAAV4E. Six weeks after administration of the same dose vector (1 × 10¹³ vg/kg), both the MyoAAV vectors demonstrated remarkably greater transduct

SUBMITTER: Liao KA 

PROVIDER: S-EPMC12419012 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature