Barry J Byrne, MD, PhD, on the Potential of Directed Evolution to Improve AAV Gene Therapy

This is the third part of an interview with Barry J Byrne, MD, PhD. For the first part, click here.

“...This field has really accelerated in the last few years and I'm particularly hopeful that we'll continue to find new ways to manufacture these products at lower cost, improve the efficiency of delivery, and lower doses for the purpose of easily accessible therapies that are going to even have a greater impact in the future.”

Currently, several FDA-approved gene therapies, and many of those currently in clinical or preclinical development, deliver their genetic payload via adeno-associated virus (AAV) vectors. Although these AAV capsids have demonstrated sufficient safety and efficacy for some indications, their tropism towards the organ or system most closely associated with the disease itself is often limited. As such, there is a great interest in either using alternative delivery methods for gene therapy, such as nonviral approaches, or improving upon the AAV vector-based approach through the discovery and development of novel capsids. In the latter approach, directed evaluation may be used to develop AAV capsids with tropism for a specific cell type, such as muscle cells.

As part of a larger discussion with Barry J Byrne, MD, PhD, the chief medical advisor of Muscular Dystrophy Association (MDA) and a physician-scientist at the University of Florida, about the upcoming Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, which will be held on March 3-6, 2024, in Orlando, Florida, CGTLive™ asked Byrne about what he sees for the future of gene therapy in general and what he expects will be a focus of development in the near-term future. He spoke about the ability of directed evolution to identify myotropic AAV vectors, vectors that bind to ligands on muscle cells, and how these efforts may form the basis of the next frontier in AAV vector-based gene therapy. Byrne noted that AAV vectors that have tropism for skeletal muscle cells, cardiac muscle cells, and stem cells may be of particular importance for treating neuromuscular diseases. He emphasized the potential of genetically modifying stem cells in particular to provide long-lasting treatment effects.

Click here to register for the upcoming 2024 MDA Conference.