CRISPR-Cas9 genome editing using targeted lipid nanoparticles for cancer therapy
Daniel Rosenblum, Anna Gutkin, Ranit Kedmi, Srinivas Ramishetti, Nuphar Veiga, Ashley M. Jacobi, Mollie S. Schubert, Dinorah Friedmann‐Morvinski, Zvi R. Cohen, Mark A. Behlke, Judy Lieberman, Dan Peer
Abstract
(sgPLK1-cLNPs) into aggressive orthotopic glioblastoma enabled up to ~70% gene editing in vivo, which caused tumor cell apoptosis, inhibited tumor growth by 50%, and improved survival by 30%. To reach disseminated tumors, cLNPs were also engineered for antibody-targeted delivery. Intraperitoneal injections of EGFR-targeted sgPLK1-cLNPs caused their selective uptake into disseminated ovarian tumors, enabled up to ~80% gene editing in vivo, inhibited tumor growth, and increased survival by 80%. The ability to disrupt gene expression in vivo in tumors opens new avenues for cancer treatment and research and potential applications for targeted gene editing of noncancerous tissues.