Double-Strand Break Repair Pathways Differentially Affect Processing and Transduction by Dual AAV Vectors.

ABSTRACT: Recombinant adeno-associated viral vectors (rAAV) are a powerful tool for gene delivery but have a limited DNA carrying capacity. Efforts to expand this genetic payload have focused on engineering the vector components, such as dual trans-splicing vectors which double the delivery size by exploiting the natural concatenation of rAAV genomes in host nuclei. We hypothesized that inefficient dual vector transduction could be improved by modulating host factors which affect concatenation. Since factors mediating concatenation are not well defined, we performed a genome-wide screen to identify host cell regulators. We discovered that Homologous Recombination (HR) is inhibitory to dual vector transduction. We demonstrate that depletion or inhibition of HR factors BRCA1 and Rad51 significantly in

SUBMITTER: Maurer AC 

PROVIDER: S-EPMC10542147 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature