Intracellular delivery is critical for the introduction of therapeutics into the cell. However, most delivery systems are hindered due to endosomal entrapment of delivery cargo. Previous work in our lab has demonstrated supramolecular nanoparticle-protein delivery systems which can provide successful delivery of protein cargo directly to the cytosol. This has notably been applied for the cellular introduction of the recombinant CRISPR/Cas9 machinery. The inclusion of a 'donor' DNA template would allow for this delivery system to perform genetic knock-in, but the co-delivery of protein and plasmid has proven challenging. Through the pre-incubation of PONI-C3-Guan polymer and protein, assemblies were formed by coating plasmid DNA on the exterior of the assembly. Using these assemblies, effective co-delivery of plasmid DNA and protein was demonstrated in cultured mammalian cells, offering potential for therapeutic translatability.

Direct co-delivery of supramolecular nanoparticle-protein assemblies for genetic knock-in

2019 Fall National Meeting

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