Delivery of CRISPR/Cas9 Plasmids by Cationic Gold Nanorods: Impact of the Aspect Ratio on Genome Editing and Treatment of Hepatic Fibrosis

Delivery of CRISPR/Cas9 machineries into living cells and tissues is of paramount importance in a wide range of therapeutic applications, yet the shortage of delivery vectors that can efficiently deliver large CRISPR/Cas9 plasmids has severely impeded its applications from complicated and diverse genome-editing contexts. Herein, we demonstrate that cationic polymer-coated gold nanorods (AuNRs) with a high aspect ratio AR exhibit a unique manner to assemble DNA, excellent capability to mediate internalization, and strong ability to escape endosomes. The intracellular delivery mediated by cationic nanorods of a high AR enables Cas9-mediated genome editing and dCas9-mediated transcriptional activation, and in vivo delivery of CRISPR/Cas9 plasmid-targeting Fas by cationic AuNRs can successfully protect the mice from liver fibrosis. The current study reveals how nanomaterials with a particular structure contribute to genome-editing activity and defines a new method for the efficient delivery of CRISPR/Cas9 plasmids.