Active immunoprophylaxis and vaccine augmentations mediated by a novel plasmid DNA formulation.

Plasmid DNA (pDNA) gene delivery is a highly versatile technology which has the potential to address a multitude of unmet medical needs. Advances in the pDNA delivery to host tissue with the employment of in vivo electroporation (EP) has led to significantly enhanced gene expression leading to the recent demonstration of clinical efficacy with the platform. Building upon this platform, we report enzyme-mediated modification of the muscle tissue extracellular matrix structure at the site of pDNA delivery operates in a synergistic manner with EP to further enhance both local and systemic gene expression. Specifically, administration of chondroitinase ABC (Cho ABC) to the site of intramuscular delivery of pDNA led to transient disruption of chondroitin sulfate scaffolding barrier permitting enhanced gene distribution and expression across the tissue. The employment of Cho ABC in combination with CELLECTRA® IM EP resulted in increased gene expression by 5.5-fold in mice and 17.98-fold in rabbits. We demonstrated how this protocol can be universally applied to an active prophylaxis platform to increase the in vivo production of functional IgG, and to DNA vaccine protocols to permit drug dose sparing. Our data indicate Cho ABC formulation to be of significant value upon combination with EP to drive enhanced gene expression levels in pDNA delivery protocols.