Reengineering a receptor footprint of adeno-associated virus enables selective and systemic gene transfer to muscle.

Published

Journal Article

Reengineering the receptor footprints of adeno-associated virus (AAV) isolates may yield variants with improved properties for clinical applications. We generated a panel of synthetic AAV2 vectors by replacing a hexapeptide sequence in a previously identified heparan sulfate receptor footprint with corresponding residues from other AAV strains. This approach yielded several chimeric capsids displaying systemic tropism after intravenous administration in mice. Of particular interest, an AAV2/AAV8 chimera designated AAV2i8 displayed an altered antigenic profile, readily traversed the blood vasculature, and selectively transduced cardiac and whole-body skeletal muscle tissues with high efficiency. Unlike other AAV serotypes, which are preferentially sequestered in the liver, AAV2i8 showed markedly reduced hepatic tropism. These features of AAV2i8 suggest that it is well suited to translational studies in gene therapy of musculoskeletal disorders.

Full Text

Duke Authors

Cited Authors

  • Asokan, A; Conway, JC; Phillips, JL; Li, C; Hegge, J; Sinnott, R; Yadav, S; DiPrimio, N; Nam, H-J; Agbandje-McKenna, M; McPhee, S; Wolff, J; Samulski, RJ

Published Date

  • January 2010

Published In

Volume / Issue

  • 28 / 1

Start / End Page

  • 79 - 82

PubMed ID

  • 20037580

Pubmed Central ID

  • 20037580

Electronic International Standard Serial Number (EISSN)

  • 1546-1696

Digital Object Identifier (DOI)

  • 10.1038/nbt.1599

Language

  • eng

Conference Location

  • United States