Co-injection of Hyaluronidase Enhanced Bioavailability and Expression Level of Lipid Nanoparticle Delivered mRNA

Ruiqi Shi – Research specialist, University of Pennsylvania; Drew Weissman – Roberts Family Professor in Vaccine Research, Director of the Penn Institute for RNA Innovation, Director of Vaccine Research in the Infectious Diseases Division, University of Pennsylvania

Introduction:

Messenger RNA–lipid nanoparticle (mRNA-LNP) technology enables safe and efficient in vivo delivery of mRNAs encoding prophylactic vaccines and therapeutic proteins. However, improving biodistribution and protein expression following clinically practical routes such as subcutaneous (SC) administration remains an important challenge.

Hyaluronidase (HYAL), a naturally occurring enzyme historically described as a “spreading factor,” catalyzes the degradation of hyaluronan (HA), a major component of the extracellular matrix. We hypothesized that transient enzymatic modulation of the extracellular matrix would enhance mRNA-LNP distribution and translation following SC delivery.