Enhancing the Development of AAV-Based Therapeutics With Mass Photometry

Adeno-associated viruses (AAVs) are a commonly used vector for delivering gene therapies, with over 200 AAV-based clinical trials targeting more than 60 diseases currently ongoing. These AAVs typically contain a DNA payload that encodes a therapeutic agent that silences, edits or repairs the genetic disease in a target cell type. A major challenge in the production of an AAV drug product is the removal of “empty” AAVs that lack a DNA payload and are chemically identical to their “full” counterparts carrying the therapeutic DNA. The presence of inactive, empty capsids reduces the therapeutic efficacy of the product. Therefore, the proportion of empty and full capsids (empty/full ratio) is a key analytical attribute of AAV samples. Although a range of analytical techniques can provide this information, many have important drawbacks such as requiring long analysis times, large and complex equipment or highly trained staff. These drawbacks are an obstacle to efficiently incorporating these techniques within AAV production pipelines. Mass photometry is an easy-to-use bioanalytical technology that measures the empty/full ratio of AAV capsids in minutes using nominal sample amounts and needing minimal sample preparation. As it does not require large capital expense and skilled operators, mass photometry can be readily integrated throughout development and manufacturing, quickly providing key analytical information at different stages of these processes. We present in this webinar the capabilities of the SamuxMP, a mass photometer that addresses the challenges of AAV characterization, and comment on published examples of its use for AAV characterization throughout production. We also describe the GMP software package for the SamuxMP, which supports the implementation of the SamuxMP in GMP-regulated environments.