A Different Spin on AAV: Enhancing Gene Therapy Development with the Analytical Ultracentrifuge

Adeno-associated viruses (AAVs) are under development as mechanisms of delivery for therapeutic genes to target cells since they are genetically tractable and can be administered in a way that avoids significant immune response. But despite their wide development, analysis and manufacturing of viral vectors remains a challenge.

During production, AAVs must be produced in carefully modified cell cultures, isolated, and purified through a complex, multistep process, typically with poor yields. This leaves a very small number of purified AAVs for subsequent analysis and development. This raises the costs of each batch, making AAV gene therapy development expensive and time-consuming. AAV capsid R&D must be made cheaper and more efficient to reduce drug prices and enable wider adoption of gene therapies.

More effective tools are needed to determine the empty/full ratio of capsids during R&D. Empty/full capsid characterization is crucial because empty and partially packaged capsids are ineffective in therapeutic formulations and can provoke negative immune responses. However, the process for determining empty/full ratios during R&D often leads to significant capsid loss, especially when using techniques like anion exchange or affinity chromatography.

Analytical ultracentrifugation (AUC) is an innovative technique for separating AAVs of varying genetic payloads. It offers higher resolution compared to anion exchange chromatography, reliably differentiating between empty, partially full, and full AAV capsids. AUC techniques have become well-known as a standard for measuring this critical quality attribute. Instruments like the Beckman Coulter Life Sciences Optima AUC can enable researchers to reliably separate empty and full capsids and provide sensitive data on partially packaged capsids, thereby accelerating the isolation of fully loaded AAVs for preclinical use.

Streamlining AAV analysis processes saves time and resources, contributing to the possibility of low-cost gene therapies. To explore more advanced tools that can optimize processes in your lab, contact an expert at Danaher's Life Sciences companies today.