Voyager’s VCAP-102 Shows Broad CNS Gene Delivery Using ALPL Receptor, Enabling New Neuro Therapies

Voyager Therapeutics has announced the first peer-reviewed publication highlighting the ability of a novel AAV capsid, VCAP-102, to cross the blood-brain barrier (BBB) via the alkaline phosphatase (ALPL) receptor. Published in Molecular Therapy, the study identifies ALPL as a highly conserved vascular receptor and the key mechanism enabling efficient gene delivery across the BBB, a major challenge in treating neurological diseases.

“Understanding ALPL and its ability to mediate transport across the blood-brain barrier has been foundational to the evolution of our gene therapy programs, two of which are advancing towards IND filings this year with a partner. Building on our first-generation capsids, such as VCAP-102, which is featured in this paper, we have evolved next-generation capsids with even stronger brain transduction and liver de-targeting, as well as stealth capsids with immune-evading capabilities,” said Mathieu Nonnenmacher, Ph.D., Vice President of Gene Therapy at Voyager.

The paper outlines how VCAP-102 achieved 20- to 400-fold greater gene transfer across multiple brain regions compared to AAV9 in both rodents and non-human primates. Importantly, the capsid demonstrated cross-species activity and confirmed transcytosis with human ALPL in an in vitro cell model, suggesting strong clinical translation potential. This innovation may represent a breakthrough in delivering therapies to the central nervous system (CNS) non-invasively.

“In addition to speeding the evolution of novel capsid families, we are leveraging our work with ALPL and other receptors to deliver diverse classes of non-viral candidates into the CNS. We believe this multi-modality approach, encompassing both viral and non-viral CNS delivery, is critical to addressing unmet needs in neurological disease,” said Todd Carter, Ph.D., Chief Scientific Officer of Voyager Therapeutics.

As presented at ASGCT’s recent annual meeting, Voyager’s second-generation CNS capsids also demonstrated broad and efficient neuronal and astrocyte transduction in non-human primates after a single intravenous dose. The technology successfully targeted key brain structures implicated in neurodegenerative diseases, positioning Voyager as a leader in next-generation gene therapies for CNS disorders.