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Muscle-targeting adeno-associated virus capsid variants, recombinant adeno-associated viruses and uses thereof

PendingCN122080147AReduced enrichmentreduce doseGenetic material ingredientsMuscular disorderMuscle tissueCapsid
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.
Owner:SICHUAN UNIV