Exosome-mediated delivery of CRISPR/Cas9 for targeting of oncogenic Kras^G12D in pancreatic cancer.

ABSTRACT: CRISPR/Cas9 is a promising technology for gene editing. To date, intracellular delivery vehicles for CRISPR/Cas9 are limited by issues of immunogenicity, restricted packaging capacity, and low tolerance. Here, we report an alternative, nonviral delivery system for CRISPR/Cas9 based on engineered exosomes. We show that non-autologous exosomes can encapsulate CRISPR/Cas9 plasmid DNA via commonly available transfection reagents and can be delivered to recipient cancer cells to induce targeted gene deletion. As a proof-of-principle, we demonstrate that exosomes loaded with CRISPR/Cas9 can target the mutant Kras ^G12D oncogenic allele in pancreatic cancer cells to suppress proliferation and inhibit tumor growth in syngeneic subcutaneous and orthotopic models of pancreati

SUBMITTER: McAndrews KM 

PROVIDER: S-EPMC8321670 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature