Delivery of CRISPR/Cas9 Plasmids by Cationic Gold Nanorods: Impact of the Aspect Ratio on Genome Editing and Treatment of Hepatic Fibrosis
Yuxuan Chen, Xiaohong Chen, Di Wu, Huhu Xin, Desui Chen, Da Li, Hongming Pan, Chang‐Xin Zhou, Ping Yuan
Abstract
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.