Cross-Packaging and Capsid Mosaic Formation in Multiplexed AAV Libraries.

ABSTRACT: Generation and screening of libraries of adeno-associated virus (AAV) variants have emerged as a powerful method for identifying novel capsids for gene therapy applications. For the majority of libraries, vast population diversity requires multiplexed production, in which a library of inverted terminal repeat (ITR)-containing plasmid variants is transfected together into cells to generate the viral library. This process has the potential to be confounded by cross-packaging and mosaicism, in which particles are comprised of genomes and capsid monomers derived from different library members. Here, we investigate the prevalence of cross-packaging and mosaicism in simplified, minimal libraries using novel assays designed to assess capsid composition and packaging fidelity. We show that AAV lib

SUBMITTER: Schmit PF 

PROVIDER: S-EPMC6938944 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature