RT Journal Article SR Electronic T1 Exosome-mediated delivery of CRISPR/Cas9 for targeting of oncogenic KrasG12D in pancreatic cancer JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202000875 DO 10.26508/lsa.202000875 VO 4 IS 9 A1 Kathleen M McAndrews A1 Fei Xiao A1 Antonios Chronopoulos A1 Valerie S LeBleu A1 Fernanda G Kugeratski A1 Raghu Kalluri YR 2021 UL https://www.life-science-alliance.org/content/4/9/e202000875.abstract AB 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 KrasG12D oncogenic allele in pancreatic cancer cells to suppress proliferation and inhibit tumor growth in syngeneic subcutaneous and orthotopic models of pancreatic cancer. Exosomes may thus be a promising delivery platform for CRISPR/Cas9 gene editing for targeted therapies.