Re-designing Adeno-Associated Virus Manufacturing

Gene therapy drugs hold immense promise in curing certain diseases, but the cost and complexity of manufacturing create a significant barrier to access. In response, the Swedish consortium GeneNova was established, bringing together partners from the government, industry, and academia with the goal of making these therapies more accessible. Biotage is a key contributor to GeneNova, providing technology and expertise in plasmid DNA and adeno-associated virus (AAV) purification.

Interest in gene therapy drugs, particularly AAV-based therapies, is surging as they have the potential to revolutionize the treatment of genetic diseases. AAV manufacturing requires large amounts of high-quality plasmids, a labor-intensive and time-consuming process. Biotage’s automated plasmid purification solutions are used within the consortium with the goal of streamlining production methods.

KTH Royal Institute of Technology in Stockholm, the coordinator of GeneNova, compared the Biotage® PhyPrep System for automated plasmid purification with a commercially available manual plasmid purification kit. Their aim was to identify the best solution to produce AAV9, a serotype of interest in therapeutics and clinical trials. The plasmids were purified in gigaprep scale, with the study focusing on plasmid quality, their preparation time and AAV titers.

The automated process demonstrated a 90% reduction in manual labor time, from nine hours with the manual kit, to thirty-five minutes with Biotage® PhyPrep. The total process time was reduced by almost half. Even when running an optional precipitation step with the system, the manual labor time can be reduced by 80%. Smallscale production of AAV9 showed a remarkable twenty-fold increase in yields using PhyPrep compared to the manual kit, when using the AAV-MAX production system and HEK293 VPC2.0 cells.

The conclusion of the study was that the Biotage® PhyPrep automation significantly reduced plasmid preparation time and enhanced AAV yields. The automated plasmid purification does not only deliver potential cost savings, but also opens up avenues for accelerating gene therapy research and development, which will ultimately assist in making gene therapy drugs more accessible.

This article is from Biotage Annual Report 2023 – you can read the whole report here.