Rapid and Accurate AAV Capsid Quantification Using Multi-Angle Dynamic Light Scattering (MADLS) for In-Process Gene Therapy Manufacturing

Background & Aim: Adeno-associated viruses (AAVs) are widely utilized as vectors for gene delivery in therapeutic applications. Precise quantification of AAV capsid titers is crucial for ensuring consistent product quality and safety during manufacturing. Current methods such as ELISA, while effective, are time-consuming and involve multiple steps, including incubation and washing, which may limit their suitability for quick paced in-process sample testing.Methodology: We conducted a study to evaluate Multi-Angle Dynamic Light Scattering (MADLS) as a rapid and reliable alternative method for measuring AAV capsid titer, particle size, and aggregation. Unlike ELISA, the MADLS assay is a one-step process that requires no sample manipulation and yields results in under 10 minutes. This feature makes MADLS particularly suitable for real-time, in-process testing, enabling faster decision-making during AAV manufacturing. Results: Our findings show that MADLS provides results comparable to ELISA in terms of accuracy, while significantly reducing the time required for analysis. The method's capability to perform repeated measurements without time constraints further enhances its utility in ensuring consistent product quality across multiple stages of the production workflow. Additionally, MADLS eliminates the need for complex sample preparation, thereby reducing the potential for operator-induced variability. Conclusion: The adoption of MADLS in AAV manufacturing reflects the growing need for fast, precise, and simple nanoparticle characterization in gene therapy, pharmaceuticals, and medical applications. streamlining key analytical processes, MADLS enhances manufacturing efficiency, accelerates production timelines, improves process control, and ensures consistent product quality, ultimately enabling the faster delivery of high-quality gene therapy products to meet patient needs.