AAV ancestral reconstruction library enables selection of broadly infectious viral variants.

ABSTRACT: Adeno-associated virus (AAV) vectors have achieved clinical efficacy in treating several diseases. However, enhanced vectors are required to extend these landmark successes to other indications and protein engineering approaches may provide the necessary vector improvements to address such unmet medical needs. To generate new capsid variants with potentially enhanced infectious properties and to gain insights into AAV's evolutionary history, we computationally designed and experimentally constructed a putative ancestral AAV library. Combinatorial variations at 32 amino acid sites were introduced to account for uncertainty in their identities. We then analyzed the evolutionary flexibility of these residues, the majority of which have not been previously studied, by subjecting the library to

SUBMITTER: Santiago-Ortiz J 

PROVIDER: S-EPMC4509550 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature