Engineering liver-detargeted AAV9 vectors for cardiac and musculoskeletal gene transfer.

ABSTRACT: We report the generation of a new class of adeno-associated virus serotype 9 (AAV9)-derived vectors displaying selective loss of liver tropism and demonstrating potential for cardiac and musculoskeletal gene transfer applications. Random mutagenesis of residues within a surface-exposed region of the major AAV9 capsid protein yielded a capsid library with mutations clustered at the icosahedral threefold symmetry axis. Using a combination of sequence analysis, structural models, and in vivo screening, we identified several functionally diverse AAV9 variants. The latter were classified into three functional subgroups, with respect to parental AAV9 displaying: (i) decreased transduction efficiency across multiple tissues; (ii) a selective decrease in liver transduction, or (iii) a similar tran

SUBMITTER: Pulicherla N 

PROVIDER: S-EPMC3129791 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature