Polo-like kinase inhibitors increase AAV production by halting cell cycle progression.

ABSTRACT: Recombinant adeno-associated viruses (rAAVs) are commonly used in gene therapy for preclinical research and therapeutic applications. Despite the clinical efficacy of rAAVs, their manufacturing involves challenges in productivity and quality, leading to limited availability. In this study, we aimed to identify compounds that increase the capacity of cells to produce AAV9 with a high-throughput small-molecule screening strategy. With the Arrayed Targeted Library for AAV Screening platform, we screened a library of 3,300 small molecules and identified several targets, including cell cycle modulators, G protein-coupled receptor modulators, histone deacetylate inhibitors, Janus kinase inhibitors, and metabolic modulators. Most notably, we identified Polo-like kinase isoform 1 (PLK1) inhibitors

SUBMITTER: Fisher K 

PROVIDER: S-EPMC11834096 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature