Cancer-derived exosomes as a delivery platform of CRISPR/Cas9 confer cancer cell tropism-dependent targeting

Authors
Kim, Seung MinYang, YoosooOh, Seung JaHong, YeonsunSeo, MinkooJang, Mihue
Issue Date
2017-11-28
Publisher
ELSEVIER SCIENCE BV
Citation
JOURNAL OF CONTROLLED RELEASE, v.266, pp.8 - 16
Abstract
An intracellular delivery system for CRISPR/Cas9 is crucial for its application as a therapeutic genome editing technology in a broad range of diseases. Current vehicles carrying CRISPR/Cas9 limit in vivo delivery because of low tolerance and immunogenicity; thus, the in vivo delivery of genome editing remains challenging. Here, we report that cancer-derived exosomes function as natural carriers that can efficiently deliver CRISPR/Cas9 plasmids to cancer. Compared to epithelial cell-derived exosomes, cancer-derived exosomes provide potential vehicles for effective in vivo delivery via selective accumulation in ovarian cancer tumors of SKOV3 xenograft mice, most likely because of their cell tropism. CRISPR/Cas9-loaded exosomes can suppress expression of poly (ADP-ribose) polymerase-1 (PARP-1), resulting in the induction of apoptosis in ovarian cancer. Furthermore, the inhibition of PARP-1 by CRISPR/Cas9-mediated genome editing enhances the chemosensitivity to cisplatin, showing synergistic cytotoxicity. Based on these results, tumor-derived exosomes may be very promising for cancer therapeutics in the future.
Keywords
EXTRACELLULAR VESICLES; OVARIAN-CANCER; COMMUNICATORS; NANOCARRIERS; RESISTANCE; VEHICLES; IMMUNITY; SIRNA; PARP; EXTRACELLULAR VESICLES; OVARIAN-CANCER; COMMUNICATORS; NANOCARRIERS; RESISTANCE; VEHICLES; IMMUNITY; SIRNA; PARP; CRISPR/Cas9; Gene editing; Cancer therapy, combination therapy; Delivery vehicle; Exosomes; PARP-1; Cisplatin
ISSN
0168-3659
URI
https://pubs.kist.re.kr/handle/201004/122037
DOI
10.1016/j.jconrel.2017.09.013
Appears in Collections:
KIST Article > 2017
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