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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

261 Scopus citations


Harnessing CRISPR-Cas9 technology for cancer therapeutics has been hampered by low editing efficiency in tumors and potential toxicity of existing delivery systems. Here, we describe a safe and efficient lipid nanoparticle (LNP) for the delivery of Cas9 mRNA and sgRNAs that use a novel amino-ionizable lipid. A single intracerebral injection of CRISPR-LNPs against PLK1 (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.

Original languageEnglish
Article numberabc9450
JournalScience advances
Issue number47
StatePublished - 18 Nov 2020


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