Efficient Cytosolic Delivery of siRNA Using Nanoparticle-Stabilized Nanocapsules

Vincent M. Rotello, Ph.D.

•       Novel delivery vehicle for the development and delivery of RNAi-based therapeutics

•       Advanced tool for life science, drug discovery or biomedical research

•       Efficient intracellular nucleic acid delivery system

•       New mechanism of siRNA delivery that allows for efficient and rapid cytosolic delivery of siRNA

•       No endosomal entrapment of siRNA

•       Stable nanocapsules

•       High-efficiency gene silencing

•       Applicable to the cytosolic delivery of other nucleic acids

This invention provides a new siRNA delivery vehicle that enables efficient cytosolic delivery of siRNA as well as other nucleic acids. The delivery system involves the use of surface functionalized nanoparticles to form self-assembled superstructures with the protein to be delivered. The nanoparticle-protein assemblies effectively escape endosomal entrapment and rapidly deliver the protein into the cell cytosol or the targeting organelle. This protein delivery system has been successfully demonstrated for the efficient delivery of the CRISPR/Cas9 gene editing system as well as a number of other proteins with different physiochemical properties.

Nanocapsule-based siRNA delivery resulted in efficient knockdown of PLK1 protein in cancer cells