Adeno-associated virus (AAV) vectors are key materials in many gene therapies, yet how recombinant AAV production is regulated within producer cells—including vector genome packaging efficiency and yield—still isn’t well understood. To address this challenge, we developed a high-content, modular genetic screening platform that can evaluate hundreds of plasmid designs in a few weeks.

Our approach pairs combinatorial design with advanced analytics to evaluate how diverse genetic elements influence AAV production. Using this platform, we identified several design combinations that enhance vector genome titer and packaging efficiency, leading to marked increases in vector titers and fullness. These findings provide helpful insights into the molecular determinants of how AAV vectors are regulated and offer a useful tool to optimize AAV production processes to meet the growing demands of gene therapy candidates in the clinic.