Engineering novel AAV capsids by broadly attenuated and subsequent muscle-specific tropism in mice and NHPs - PubMed
6 hours ago
- #gene therapy
- #muscle-specific tropism
- #AAV capsids
- A two-step capsid engineering strategy was developed to create novel AAV vectors with improved muscle-specific tropism.
- AAV.Zero1, AAV.Zero2, and AAV.Zero3 capsids were engineered with reduced or abolished broad transduction.
- Insertion of a myogenic peptide into AAV.Zero3 produced AAV.eM, which showed robust muscle-specific expression.
- AAV.eM demonstrated minimal off-target transduction in organs like liver, lung, brain, and kidney.
- AAV.eM performed consistently in two mouse strains and non-human primates.
- AAV.eM achieved expression levels similar to MyoAAV 4A but with a superior safety profile.
- AAV.eM functionally rescued a mouse model of Duchenne muscular dystrophy using micro-dystrophin gene delivery.
- The study establishes AAV.eM as an improved myotropic vector and proof of concept for a capsid engineering platform.