Engineeringthe Next
Standard of Care

Hyaluronidase-enhanced delivery in gene therapy and regenerative medicine for improved vector, cell, and cargo access

Frontiers in Drug Delivery

Efficient delivery of gene therapy vectors and regenerative cargo to the central nervous system (CNS) is limited by the hyaluronic acid (HA)-rich extracellular matrix (ECM). Hyaluronidase enzymes transiently depolymerize HA, reducing tissue viscosity and increasing interstitial permeability through a well-defined, reversible mechanism. This narrative review synthesizes the mechanistic basis, evidence tiers, dosing and technique protocols, safety considerations, and translational knowledge gaps for hyaluronidase as a CNS delivery adjunct.

Patrick E. Sewell, Christopher Jensen