Damien Maura, PhD, on AAV Capsids That Evade Neutralizing Antibodies

“In the field of AAV gene therapy, there is between 30% and 65% of patients who cannot receive an AAV gene therapy treatment due to the presence of neutralizing antibodies. The goal of our work was to try and find a solution for that problem.”

Over the past few years, adeno-associated virus (AAV) vector-based gene therapy has gained a foothold as a key gene therapy modality, and it is currently represented by several FDA-approved products and numerous investigational therapeutic candidates. Although AAV vector-based gene therapies have transformative potential for some indications, a substantial number of patients may be unable to receive these products because they have preexisting immunity to the AAV capsid in use by a particular therapy.

Voyager Therapeutics is currently seeking to overcome this challenge through the development of novel AAV capsids that target the central nervous system and are able to evade the body’s immune response. Notably, Damien Maura, PhD, a senior scientist at Voyager, presented preclinical research on this topic at the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting, held May 13 to 17, 2025, in New Orleans, Louisiana.

At the conference, CGTLive® sat down with Maura to learn more. Maura explained that using the company's proprietary Tropism Redirection of AAV by Cell-type-specific Expression of RNA (TRACER) technology, Voyager redesigned capsid surfaces to remove antibody epitopes in order to improve immune evasion.

Maura highlighted the discovery of a third-generation TRACER capsid that preserves the brain transduction efficiency and cellular tropism of its parent capsid while adding mutations for antibody resistance. He also pointed out that machine learning models further identified additional mutations that could enhance both brain transduction and immune evasion.

Maura emphasized that although these findings are promising, translation to humans remains the biggest unknown until clinical trials begin. He also touched on Voyager’s future plans for the technology, which will focus on further expanding patient eligibility by incorporating additional mutations to capsid epitopes.

Click here to view more coverage of the 2025 ASGCT Annual Meeting.