Practical process development strategies to prepare AAV downstream operations for manufacturing

While AAV vectors hold significant promise for gene therapy, their complex capsid structure, propensity to form empty capsids lacking a therapeutic transgene, and sensitivity to process parameters create manufacturing challenges. Urgent patient needs and accelerated timelines to reach the clinic provide limited window for process optimization, adding complexity for process developers. To navigate these constraints, we explore practical development approaches to improve downstream purification efficiency and enhance platform compatibility. We examine affinity capture chromatography by characterizing the relationship between binding capacity, feed concentration, and process time. In certain scenarios, implementing tangential flow filtration prior to affinity capture significantly benefits process time, resin utilization, and scheduling logistics. We also investigate anion exchange chromatography for separating empty and full capsids, highlighting a strong correlation between chromatogram peak area and elution pool titer. This scalable correlation supports real-time product quantification, enhancing process understanding to enable data-driven decisions during AAV manufacturing.

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