Sven Moller-Tank, PhD, on Regeneron’s Precision Approach to AAV Targeting

“We are going after a particular receptor and then engineering our capsids to target that receptor. I think that's a unique approach. We're one of the first, I think, to successfully show that this can work in vivo.”

CGTLive® spoke with Sven Moller-Tank, PhD, a senior director at Regeneron, at the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting, held May 13 to 17, 2025, in New Orleans, Lousiana. He detailed how the company is advancing a receptor-driven strategy to improve gene therapy targeting, one grounded in antibody expertise rather than random library screening. His team is developing antibody/adeno-associated virus (AAV) fusion platforms to precisely direct gene therapy payloads to specific tissues, including skeletal muscle, the central nervous system (CNS), and peripheral nervous system. This could build on Regeneron’s efforts in genetic medicine, where the company is applying cross-disciplinary efforts to develop new therapeutic candidates.

Moller-Tank noted that while others in the field are retroactively identifying receptor interactions post hoc, Regeneron’s method starts with the receptor in mind. This enables more predictable biodistribution and may reduce immune complications, such as off-target effects or preexisting immunity. At the meeting, he discussed platforms designed to target the transferrin receptor for CNS delivery, CACNG1 for skeletal muscle, and p75 for peripheral neurons. His team is also refining capsid-antibody constructs for both covalent and bispecific formats, with new preclinical findings in nonhuman primates validating these constructs, particularly in skeletal muscle and CNS models.

This in vivo success marks a turning point in the field’s evolution toward not targeting the liver and mitigating off-target toxicities. Regeneron’s efforts also extend beyond AAV, with early progress applying this targeted delivery system to siRNA, lipid nanoparticles, and other modalities. As these platforms advance, they may change how therapies are delivered across different treatment types. With gene therapy’s challenges more visible than ever, Moller-Tank believes this precision-first approach may help unlock its full potential.

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