期刊
LIFE SCIENCE ALLIANCE
卷 4, 期 9, 页码 -出版社
LIFE SCIENCE ALLIANCE LLC
DOI: 10.26508/lsa.202000875
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资金
- MD Anderson Cancer Center
- Odyssey Program
- Theodore N. Law for Scientific Achievement at The University of Texas MD Anderson Cancer Center
CRISPR/Cas9 technology shows promise for gene editing, and exosomes engineered as non-viral delivery systems can successfully deliver CRISPR/Cas9 for targeted gene editing in cancer cells, demonstrating potential therapeutic applications.
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 pancreatic cancer. Exosomes may thus be a promising delivery platform for CRISPR/Cas9 gene editing for targeted therapies.
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