Successful Scale-Up Validation Of A Small-Molecule Compound For Increased AAV Yields

By R. Derler, C. Reid, F. Sonntag, M. Mandegar, M. Hoerer, and A. Schulze

Recombinant adeno-associated virus (rAAV) is the most widely used viral vector for in vivo gene therapy today. However, a major challenge remains the cost-efficient production of high-quality vectors that meet safety and efficacy requirements in an increasingly complex regulatory landscape.

To address this, we implemented a high-throughput small molecule screening strategy in HEK293 cells using the ATLAS (Arrayed Targeted Library for AAV Screening) platform to identify compounds that enhance rAAV production. Through shake flask studies, we identified compound SM-016, which significantly increases rAAV yields in a robust, dose-dependent manner.

Here, we present validation data from controlled bioreactor studies, demonstrating the scalability of SM-016 using the Ambr® 15 bioreactor system. Our results confirm a consistent increase in rAAV yields without compromising critical quality attributes when applying an optimized supplementation strategy, supporting the analytical comparability of vectors produced with this next-generation manufacturing platform.