Viral vectors with modified transduction profiles and methods of making and using the same

摘要

The present invention provides AAV capsid proteins, virus capsids comprising said capsid proteins and virus vectors comprising said capsid proteins, wherein the AAV capsid proteins have one or more mutations, wherein the mutation(s) result in a phenotype of decreased liver transduction and/or reduced glycan binding affinity as compared to a control. The invention also provides methods of administering the virus vectors and virus capsids of the invention to a cell or to a subject.

主权项

1. A Clade F adeno-associated virus (AAV) capsid protein, wherein the capsid protein comprises a substitution in one or more of amino acids N498, S499, E500, F501, A502, W503 and P504 (according to AAV9 VP1 numbering), in any combination, wherein the substitution in the capsid protein results in a Clade F viral phenotype of decreased transduction of liver cells as compared to a Clade F control or wild-type virus.