Naturally occurring singleton residues in AAV capsid impact vector performance and illustrate structural constraints.

ABSTRACT: Vectors based on the adeno-associated virus (AAV) are attractive and versatile vehicles for in vivo gene transfer. The virus capsid is the primary interface with the cell that defines many pharmacological, immunological and molecular properties. Determinants of these interactions are often restricted to a limited number of capsid amino acids. In this study, a portfolio of novel AAV vectors was developed after a structure-function analysis of naturally occurring AAV capsid isolates. Singletons, which are particular residues on the AAV capsid that were variable in otherwise conserved amino acid positions, were found to impact on vector's ability to be manufactured or to transduce. Data for those residues that mapped to monomer-monomer interface regions on the particle structure suggested a r

SUBMITTER: Vandenberghe LH 

PROVIDER: S-EPMC2795093 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature