Manufacturing Of A Broad Range Of AAV Capsids Using Our Suspension Platform

By E. Schweigert, R. Derler, M. Ohme, S. Henze, K. Breunig, M. Haubner, F. Dunker, M. Hoerer, A. Schulze, and F. Sonntag

A wide variety of naturally occurring and synthetically engineered adeno-associated virus (AAV) capsid sequences have been described to date. Here, we present a comprehensive comparison of several AAV capsids—including AAV1, AAV2, AAV3B, AAV8, and AAV9—produced using our optimized suspension platform process. This study focused on evaluating yield and quality parameters, both of which are heavily influenced by the design and selection of biological starting materials as well as the upstream production process. To facilitate a thorough comparison, we employed a panel of advanced analytical methods to assess a broad range of attributes across the capsids.

Our findings highlight that yield and quality metrics can vary significantly between different AAV capsids, impacting overall manufacturability. These differences underscore the need for a modular and adaptable manufacturing platform that can address the unique requirements of various AAV products.

The manufacturability of the tested capsids was successfully demonstrated using the Ambr 15 platform, a small-scale bioreactor system that has been shown to accurately predict performance at larger production scales (currently up to 200 liters within our manufacturing capabilities).

At the core of our process is a proprietary HEK293 cell line and a split two-plasmid system. This robust suspension platform has been carefully developed and optimized to maximize yields while ensuring the highest possible quality. Additionally, the platform offers full scalability, making it suitable for both small-scale research and large-scale clinical or commercial production.