Improving AAV Manufacturing: Advancements In Full Capsid Enrichment

By Chantelle Gaskin, field applications scientist, Thermo Fisher Scientific

As adeno-associated virus (AAV) manufacturing continues to mature, downstream purification strategies are evolving beyond a narrow focus on polishing to a more integrated approach to full capsid enrichment. Rather than viewing anion exchange chromatography (AEX) as a standalone separation step, developers increasingly recognize that enrichment outcomes are shaped by decisions made throughout the purification workflow, including affinity capture, buffer chemistry, load conditioning, conductivity, and elution strategy. Recent research demonstrates that optimizing salt composition, electrostatic conditions, and feed preparation can significantly improve separation performance, while modest enrichment achieved during capture may reduce the burden on downstream polishing.

Serotype- and construct-specific variability, particularly in AAV9, limits the feasibility of one-size-fits-all platform processes and reinforces the need for adaptable process development strategies. In parallel, chromatography-based approaches continue to replace ultracentrifugation and other legacy methods because they offer greater scalability, reproducibility, and compatibility with GMP manufacturing. Advances in resin and prepacked column technologies further support efficient scale-up while reducing operational variability. Together, these developments position full capsid enrichment as a coordinated process design challenge rather than a single unit operation, enabling manufacturers to build robust, transferable purification workflows that improve product quality, support commercial-scale production, and better meet evolving regulatory and manufacturing expectations.