Artificial Virus Delivers CRISPR-Cas9 System for Genome Editing of Cells in Mice
Abstract
CRISPR-Cas9 has emerged as a versatile genome-editing platform. However, due to the large size of the commonly used CRISPR-Cas9 system, its effective delivery has been a challenge and limits its utility for basic research and therapeutic applications. Herein, a multifunctional nucleus-targeting "core-shell" artificial virus (RRPHC) was constructed for the delivery of CRISPR-Cas9 system. The artificial virus could efficiently load with the CRISPR-Cas9 system, accelerate the endosomal escape, and promote the penetration into the nucleus without additional nuclear-localization signal, thus enabling targeted gene disruption. Notably, the artificial virus is more efficient than SuperFect, Lipofectamine 2000, and Lipofectamine 3000. When loaded with a CRISPR-Cas9 plasmid, it induced higher targeted gene disruption efficacy than that of Lipofectamine 3000. Furthermore, the artificial virus effectively targets the ovarian cancer via dual-receptor-mediated endocytosis and had minimum side effects. When loaded with the Cas9-hMTH1 system targeting MTH1 gene, RRPHC showed effective disruption of MTH1 in vivo. This strategy could be adapted for delivering CRISPR-Cas9 plasmid or other functional nucleic acids in vivo.
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Li et al.'s core-shell artificial virus induced higher targeted gene disruption efficacy than Lipofectamine 3000 in vitro and inhibited ovarian tumor progression in vivo.
“This system induced higher targeted gene disruption efficacy than that of Lipofectamine 3000 in vitro. After intraperitoneal administration, they also showed effective disruption of targeted MTH1 gene and significantly inhibited the progression of ovarian tumor in vivo (Fig. 4A) [117].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [117]
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- Authors
- Li, L., Song, L., Liu, X., Yang, X., Li, X., He, T., Wang, N., Yang, S., Yu, C., Yin, T., Wen, Y., He, Z., Wei, X., Su, W., Wu, Q., Yao, S., Gong, C., & Wei, Y.
- Affiliations
- Sichuan University (CN)
- Nankai University (CN)
- Corresponding author
- Yao, Shaohua
- Gong, Changyang
- Wei, Yuquan
- ORCID
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-11-17
- Volume
- 11
- Issue
- 1
- Pages
- 95-111
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- OpenAlex
- W2552166386
- Cited by
- 244
- References
- 56
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 14 · 2023: 22 · 2022: 34 · 2021: 34 · 2020: 35 · 2019: 33 · 2018: 33 · 2017: 13 · 2016: 1
- FWCI
- 14.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Nano (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Sichuan University (2015SCU04A42)
- National Natural Science Foundation of China (81372143)
- National High Technology Research and Development Program of China (2015AA020309)
- National Young Top-notch Talent Program of China
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- CRISPR/Cas9 delivery, genome editing, nuclear targeting, endosomal escape, ovarian cancer, in vivo gene editing, nucleic acid delivery
- MeSH terms
- Gene Editing, Animals, Drug Carriers, Genetic Vectors, Humans, Hyaluronic Acid, Mice, Inbred BALB C, Mice, Nude, Neoplasm Transplantation, Phosphoric Monoester Hydrolases, Plasmids, Polyethylene Glycols, Viruses, Gene Transfer Techniques, DNA Repair Enzymes, Cell Line, Tumor, CRISPR-Cas Systems, Heterografts, Drug Liberation
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