Enhancing AAV Production Using High-Throughput Screens And Rational Design

By Mo Mandegar, dPhil - Vice President and Head of Site, Alameda

Adeno-associated viruses (AAVs) have become the preferred vectors for gene therapy, offering a nonpathogenic safety profile and an expanding range of engineered capsids for targeted delivery. Despite their promise of durable, potentially curative single-dose treatments, AAV therapies face significant manufacturing challenges in scalability, yield, and quality. Current production methods, reliant on transient transfection of HEK293 cells, are hindered by inefficiencies, variability across serotypes, and high production costs.

Ascend addresses these challenges with a novel integrative approach combining high-throughput screening, transcriptomics, and rational design. Using our proprietary Arrayed Targeted Libraries for AAV Screening platform, we identify AAV enhancers to improve yield and quality. These insights inform next-generation processes, including optimized media formulations, genetic modifications of producer cell lines, and intensified production methods. By merging advanced technologies with traditional paradigms, Ascend is advancing scalable and cost-effective AAV manufacturing to meet the growing demand for gene therapies and unlock their full therapeutic potential.