The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Cancer-derived exosomes as a delivery platform of CRISPR/Cas9 confer cancer cell tropism-dependent targeting
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In another case, CRISPR/Cas9 technology has been loaded into synthetic exosomes to specifically target cancerous cells for gene editing, offering a potential new approach to treating genetic disorders and certain types of cancers [45].”
From Emerging role of exosomes in cancer therapy: progress and challenges (2025) · cites this paper as [45]
In the citing paper
“The CRISPR/Cas9-loaded exosomes significantly down-regulated PARP-1 expression, thus causing ovarian cancer cell death [54].”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [54]
Citations
Cites
A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity
Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., & Charpentier, E. (2012) · Science · doi:10.1126/science.1225829 · Cited by 17,116
Development and Applications of CRISPR-Cas9 for Genome Engineering
Hsu, P. D., Lander, E. S., & Zhang, F. (2014) · Cell · doi:10.1016/j.cell.2014.05.010 · Cited by 5,762
Exosomes: composition, biogenesis and function
Théry, C., Zitvogel, L., & Amigorena, S. (2002) · Nature reviews. Immunology · doi:10.1038/nri855 · Cited by 5,478
Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes
Alvarez-Erviti, L., Seow, Y., Yin, H., Betts, C., Lakhal, S., & Wood, M. J. A. (2011) · Nature Biotechnology · doi:10.1038/nbt.1807 · Cited by 4,930
DNA targeting specificity of RNA-guided Cas9 nucleases
Hsu, P. D., Scott, D. A., Weinstein, J. A., Ran, F. A., Konermann, S., Agarwala, V., Li, Y., Fine, E. J., Wu, X., Shalem, O., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2647 · Cited by 4,741
Inhibition of Poly(ADP-Ribose) Polymerase in Tumors from BRCA Mutation Carriers
Fong, P. C., Boss, D. S., Yap, T. A., Tutt, A., Wu, P., Mergui-Roelvink, M., Mortimer, P., Swaisland, H., Lau, A., O'Connor, M. J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0900212 · Cited by 3,634
CRISPR-Cas systems for editing, regulating and targeting genomes
Sander, J. D., & Joung, J. K. (2014) · Nature Biotechnology · doi:10.1038/nbt.2842 · Cited by 3,153
Advances and Challenges of Liposome Assisted Drug Delivery
Sercombe, L., Veerati, T., Moheimani, F., Wu, S. Y., Sood, A. K., & Hua, S. (2015) · Frontiers in Pharmacology · doi:10.3389/fphar.2015.00286 · Cited by 2,672
Exosome and Exosomal MicroRNA: Trafficking, Sorting, and Function
Zhang, J., Li, S., Li, L., Li, M., Guo, C., Yao, J., & Mi, S. (2015) · Genomics, Proteomics & Bioinformatics · doi:10.1016/j.gpb.2015.02.001 · Cited by 1,901
Systemically Injected Exosomes Targeted to EGFR Deliver Antitumor MicroRNA to Breast Cancer Cells
Ohno, S.-I., Takanashi, M., Sudo, K., Ueda, S., Ishikawa, A., Matsuyama, N., Fujita, K., Mizutani, T., Ohgi, T., Ochiya, T., et al. (2013) · Molecular Therapy · doi:10.1038/mt.2012.180 · Cited by 1,666
Polymers for Drug Delivery Systems
Liechty, W. B., Kryscio, D. R., Slaughter, B. V., & Peppas, N. A. (2010) · Annual Review of Chemical and Biomolecular Engineering · doi:10.1146/annurev-chembioeng-073009-100847 · Cited by 1,608
Exosomes: Therapy delivery tools and biomarkers of diseases
Barile, L., & Vassalli, G. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.02.020 · Cited by 1,053
The PARP Side of the Nucleus: Molecular Actions, Physiological Outcomes, and Clinical Targets
Krishnakumar, R., & Kraus, W. L. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.06.017 · Cited by 877
Iniparib plus Chemotherapy in Metastatic Triple-Negative Breast Cancer
O'Shaughnessy, J., Osborne, C., Pippen, J. E., Yoffe, M., Patt, D., Rocha, C., Koo, I. C., Sherman, B. M., & Bradley, C. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1011418 · Cited by 817
Johnsen, K. B., Gudbergsson, J. M., Skov, M. N., Pilgaard, L., Moos, T., & Duroux, M. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.04.005 · Cited by 704
Differential fates of biomolecules delivered to target cells via extracellular vesicles
Kanada, M., Bachmann, M. H., Hardy, J. W., Frimannson, D. O., Bronsart, L. L., Wang, A., Sylvester, M. D., Schmidt, T. L., Kaspar, R. L., Butte, M. J., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1418401112 · Cited by 475
Mechanisms of resistance to therapies targeting BRCA-mutant cancers
Lord, C. J., & Ashworth, A. (2013) · Nature Medicine · doi:10.1038/nm.3369 · Cited by 467
Robbins, M., Judge, A. D., & MacLachlan, I. (2009) · Oligonucleotides · doi:10.1089/oli.2009.0180 · Cited by 463
Wang, J., Hendrix, A., Hernot, S., Lemaire, M., Bruyne, E. D., Valckenborgh, E. V., Lahoutte, T., Wever, O. D., Vanderkerken, K., & Menu, E. (2014) · Blood · doi:10.1182/blood-2014-03-562439 · Cited by 449
Karikó, K., Bhuyan, P. K., Capodici, J., & Weissman, D. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.11.6545 · Cited by 446
An update on PARP inhibitors—moving to the adjuvant setting
Sonnenblick, A., de Azambuja, E., Azim, H. A., & Piccart, M. J. (2014) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2014.163 · Cited by 390
Vyas, S., Cataldo, M., Kwan, T. T., Huang, Y.-H., & Chang, P. (2013) · Nature Communications · doi:10.1038/ncomms3240 · Cited by 334
Biological Gene Delivery Vehicles: Beyond Viral Vectors
Seow, Y., & Wood, M. J. A. (2009) · Molecular Therapy · doi:10.1038/mt.2009.41 · Cited by 331
The Roles of Tumor-Derived Exosomes in Cancer Pathogenesis
Yang, C., & Robbins, P. D. (2011) · Clinical and Developmental Immunology · doi:10.1155/2011/842849 · Cited by 322
Exosomes and Other Extracellular Vesicles: The New Communicators in Parasite Infections
Coakley, G., Maizels, R. M., & Buck, A. H. (2015) · Trends in Parasitology · doi:10.1016/j.pt.2015.06.009 · Cited by 315
Exosomes as nucleic acid nanocarriers
van den Boorn, J. G., Daßler, J., Coch, C., Schlee, M., & Hartmann, G. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.06.011 · Cited by 285
Going beyond the liver: progress and challenges of targeted delivery of siRNA therapeutics
Lorenzer, C., Dirin, M., Winkler, A.-M., Baumann, V., & Winkler, J. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.02.003 · Cited by 284
Microvesicle-mediated RNA Molecule Delivery System Using Monocytes/Macrophages
Akao, Y., Iio, A., Itoh, T., Noguchi, S., Itoh, Y., Ohtsuki, Y., & Naoe, T. (2010) · Molecular Therapy · doi:10.1038/mt.2010.254 · Cited by 253
Zlotogorski‐Hurvitz, A., Dayan, D., Chaushu, G., Korvala, J., Salo, T. A., Sormunen, R. T., & Vered, M. (2014) · Journal of Histochemistry & Cytochemistry · doi:10.1369/0022155414564219 · Cited by 197
Predictive biomarkers for cancer therapy with PARP inhibitors
Michels, J., Vitale, I., Saparbaev, M. K., Castedo, M., & Kroemer, G. (2013) · Oncogene · doi:10.1038/onc.2013.352 · Cited by 117
Molecular Pathways: Targeting PARP in Cancer Treatment
Do, K. T., & Chen, A. P. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-0163 · Cited by 111
Resistance to PARP-Inhibitors in Cancer Therapy
Montoni, A., Robu, M., Pouliot, É., & Shah, G. M. (2013) · Frontiers in Pharmacology · doi:10.3389/fphar.2013.00018 · Cited by 107
In Vivo Delivery Systems for Therapeutic Genome Editing
Wang, L., Li, F., Dang, L., Liang, C., Wang, C., He, B., Liu, J., Li, D., Wu, X., Xu, X., et al. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17050626 · Cited by 101
The role of poly(ADP-ribosyl)ation in DNA damage response and cancer chemotherapy
Li, M., & Yu, X. (2014) · Oncogene · doi:10.1038/onc.2014.295 · Cited by 99
Ruiss, R., Jochum, S., Mocikat, R., Hammerschmidt, W., & Zeidler, R. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025294 · Cited by 73
CRISPR-Cas9: a promising tool for gene editing on induced pluripotent stem cells
Kim, E. J., Kang, K. H., & Ju, J. H. (2017) · The Korean Journal of Internal Medicine · doi:10.3904/kjim.2016.198 · Cited by 58
BRCA1- and BRCA2-related mutations: therapeutic implications in ovarian cancer
Pothuri, B. (2013) · Annals of Oncology · doi:10.1093/annonc/mdt307 · Cited by 50
PARP-1 may be involved in angiogenesis in epithelial ovarian cancer
Wei, W., Li, Y., Lv, S., Zhang, C., & Tian, Y. (2016) · Oncology Letters · doi:10.3892/ol.2016.5226 · Cited by 46
PARP inhibitors in BRCA1/BRCA2 germline mutation carriers with ovarian and breast cancer
Annunziata, C. M., & Bates, S. E. (2010) · F1000 Biology Reports · doi:10.3410/b2-10 · Cited by 27
Cited by
Sorted by citations
RNA delivery by extracellular vesicles in mammalian cells and its applications
O’Brien, K., Breyne, K., Ughetto, S., Laurent, L. C., & Breakefield, X. O. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0251-y · Cited by 1,811
Artificial Intelligence in Pharmaceutical Technology and Drug Delivery Design
Vora, L. K., Gholap, A. D., Jetha, K. L., Singh, T. R. R., Solanki, H. K., & Chavda, V. P. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15071916 · Cited by 1,193
The role of extracellular vesicles in cancer
Kalluri, R., & McAndrews, K. M. (2023) · Cell · doi:10.1016/j.cell.2023.03.010 · Cited by 695
Exosomes─Nature’s Lipid Nanoparticles, a Rising Star in Drug Delivery and Diagnostics
Tenchov, R., Sasso, J. M., Wang, X., Liaw, W., Chen, C., & Zhou, Q. A. (2022) · ACS Nano · doi:10.1021/acsnano.2c08774 · Cited by 642
Emerging role of exosomes in cancer progression and tumor microenvironment remodeling
Paskeh, M. D. A., Entezari, M., Mirzaei, S., Zabolian, A., Saleki, H., Naghdi, M. J., Sabet, S., Khoshbakht, M. A., Hashemi, M., Hushmandi, K., et al. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01305-4 · Cited by 591
Metadata
- Authors
- Kim, S. M., Yang, Y., Oh, S. J., Hong, Y., Seo, M., & Jang, M.
- Affiliations
- Korea Institute of Science and Technology (KR)
- Korea University (KR)
- Corresponding author
- Jang, Mihue
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2017-11
- Volume
- 266
- Pages
- 8-16
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W2754835295
- Cited by
- 481
- References
- 39
- Citations by year
- 2026: 43 · 2025: 62 · 2024: 61 · 2023: 70 · 2022: 74 · 2021: 59 · 2020: 57 · 2019: 37 · 2018: 17 · 2017: 1
- FWCI
- 12.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Funders
- KIST (2E26910)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- tumor-derived exosomes, CRISPR/Cas9 delivery, ovarian cancer, apoptosis, cisplatin sensitivity, genome editing
- MeSH terms
- Poly (ADP-Ribose) Polymerase-1, Animals, Antineoplastic Agents, Cisplatin, Combined Modality Therapy, Female, Humans, Leukocytes, Mononuclear, Mice, Inbred BALB C, Mice, Nude, Neoplasms, RNA, Genetic Therapy, Cytokines, Gene Transfer Techniques, Cell Line, Tumor, Exosomes, HEK293 Cells, CRISPR-Cas Systems
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
