Nuclease Strategies Can Cut Viral Vector Costs

The economic modeling from ArcticZymes suggests that optimized nuclease selection can double the overall process recovery for viral vectors. This approach could also slash nuclease-related costs per batch by over 70% and cut the final cost of goods per dose by an estimated 40%. The strategy centers on more effective removal of residual host cell DNA and chromatin during purification, a critical bottleneck in downstream processing. Inefficient DNA clearance can lead to filtration fouling and reduced capacity of chromatography resins, directly impacting manufacturing yield and efficiency. Traditional nucleases often show reduced activity in the salt concentrations present in bioprocessing, leading to incomplete DNA fragmentation. ArcticZymes' salt-active nucleases, like M-SAN HQ, are designed to perform optimally under these physiological salt conditions, which is especially beneficial for more fragile vectors like lentiviruses. For more robust vectors like AAVs, which can tolerate higher salt concentrations used to reduce aggregation, other specialized nucleases like SAN HQ are utilized. This tailored enzymatic approach improves downstream robustness and filtration performance, contributing to more predictable and scalable manufacturing outcomes. Regulatory agencies like the FDA and WHO have stringent limits on residual DNA in final drug products, often recommending less than 10 ng per dose with fragments smaller than 200 base pairs. Efficient nuclease digestion is therefore not just an economic optimization but also a critical step for ensuring product safety and meeting regulatory requirements. By reframing nuclease selection as a key strategic decision rather than a minor technical detail, manufacturers can unlock significant economic advantages. This is particularly crucial as the cell and gene therapy field grapples with making these transformative treatments more affordable and accessible to patients.