Unknown

Dataset Information

0

CRISPR-Cas9 genome editing using targeted lipid nanoparticles for cancer therapy.


ABSTRACT: 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.

SUBMITTER: Rosenblum D 

PROVIDER: S-EPMC7673804 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications


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 <i>PLK1</i> (sgPLK1-cLNPs) into aggressive orthotopic glioblastoma enabled up to ~70% gene editing in vivo, which caused tumor cell ap  ...[more]

Similar Datasets

| S-EPMC10823087 | biostudies-literature
| S-EPMC10671490 | biostudies-literature
| S-EPMC4978904 | biostudies-other
| S-EPMC5107994 | biostudies-literature
| S-EPMC8782450 | biostudies-literature
| S-EPMC5999541 | biostudies-literature
| S-EPMC9176214 | biostudies-literature
| S-EPMC5069954 | biostudies-literature
| S-EPMC7851445 | biostudies-literature
| S-EPMC4299274 | biostudies-other