This invention belongs to the field of
biomedical technology, specifically relating to
muscle-targeting AAV
capsid variants, recombinant AAV, and their applications. To improve the
muscle tissue transduction efficiency of AAV and reduce liver
tropism, this invention provides a
muscle-targeting AAV
capsid variant
protein, which is a polypeptide that enhances the muscle
cell or
tissue targeting of AAV
capsid protein and reduces liver
tropism by substituting, inserting, and / or deleting at least one polypeptide in the variable region VIII of the parental AAV capsid
protein VP1. Experimental results demonstrate that the AAV capsid protein variant of this invention has high transduction efficiency, significantly increases
gene expression in
muscle tissue, and possesses cross-species characteristics, enabling efficient transduction of
muscle tissue and reducing liver
tropism in mice and non-human primates. Clinical data indicate that AAVM101.μDys prepared based on the AAV capsid protein variant of this invention has good safety and
efficacy in the treatment of DMD, laying a clinical foundation for further research.