281: When Your Delivery Vehicle Contains a Membrane Protein: CMC Decisions With No Regulatory Precedent with Jitendra Kumar - Part 1

Gene therapy only works if the cargo reaches the right cells intact. Adeno-associated viruses (AAV) and lipid nanoparticles have carried the field this far, but both share a constraint: the particle is taken up into an endosome, and the payload has to escape that compartment before it is degraded. Endosomal escape is where a large share of the dose is lost, and it is why delivery, not the genetic construct, is usually the thing that limits the therapy. Lipid nanoparticles carry a second const...