Leveraging Precision Medicine In Gene Therapy: Patient Selection By Anti-AAV Total Antibody Binding

By Laura Huning, Ph.D., Staff Scientist, Companion Diagnostics (CDx)

Gene therapy offers the promise of a one-time, potentially curative treatment for a wide range of genetic disorders. The field has accelerated rapidly, with more than 4,000 gene, cell, and RNA therapies advancing through development in 2024 alone, and the pipeline continues to expand as new technological innovations emerge. A central focus for developers has been improving the safety and efficacy of these therapies by refining methods to precisely target and deliver genetic material to specific cell types.

Among the delivery systems explored, adeno-associated viral (AAV) vectors have become the most widely used in clinical trials. AAVs are uniquely capable of bypassing cellular defenses and transporting therapeutic cargo to diverse tissues with moderate specificity. Their favorable attributes — including a generally mild safety profile, broad tissue tropism, and low levels of genome integration — have established them as the leading vector platform for gene delivery.

However, despite their advantages, AAV-based therapies are not without challenges. Immune responses, dose-related toxicities, and variability in transduction efficiency highlight the importance of careful risk management strategies throughout development. Ongoing research is dedicated to engineering next-generation AAV capsids, optimizing vector design, and advancing manufacturing processes to enhance both safety and therapeutic performance. These efforts aim to unlock the full potential of AAV-mediated gene therapies and bring durable, transformative treatments to patients worldwide.