Charge-driven lipid nanoparticle encapsulation of enzymes for enhanced ERT with reduced immunogenicity

Efficient intracellular delivery of therapeutic enzymes remains a central limitation of protein-based therapies. In lysosomal storage disorders such as Pompe disease, classical enzyme replacement therapy (ERT) is particularly constrained by inefficient delivery to skeletal muscle, limited cellular uptake, and immunogenicity. Here, we introduce a lipid nanoparticle (LNP) platform designed for charge-mediated enzyme encapsulation, enabling high enzyme loading (up to 100 enzymes per LNP) while pres