Challenges in CRISPR/CAS9 delivery: potential roles of nonviral vectors
Abstract
CRISPR/Cas9 genome editing platforms are widely applied as powerful tools in basic research and potential therapeutics for genome regulation. The appropriate alternative of delivery system is critical if genome editing systems are to be effectively performed in the targeted cells or organisms. To date, the in vivo delivery of the Cas9 system remains challenging. Both physical methods and viral vectors are adopted in the delivery of the Cas9-based gene editing platform. However, physical methods are more applicable for in vitro delivery, while viral vectors are generally concerned with safety issues, limited packing capacities, and so on. With the robust development of nonviral drug delivery systems, lipid- or polymer-based nanocarriers might be potent vectors for the delivery of CRISPR/Cas9 systems. In this review, we look back at the delivery approaches that have been used for the delivery of the Cas9 system and outline the recent development of nonviral vectors that might be potential carriers for the genome editing platform in the future. The efforts in optimizing cationic nanocarriers with structural modification are described and promising nonviral vectors under clinical investigations are highlighted.
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Non-viral vectors may offer advantages over viral vectors for CRISPR/Cas9 delivery, including low immunogenicity, absence of endogenous virus recombination, less limitation in delivering larger genetic payloads, and ease of large-scale production.
“As an alternative, non-viral vectors may offer tantalizing possibility in CRISPR/Cas9 delivery with respect to their low immunogenicity, absence of endogenous virus recombination, less limitation in delivering larger genetic payloads and ease of large-scale production [73–75].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [75]
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Direct cytosolic delivery of CRISPR/Cas9-ribonucleoprotein for efficient gene editing
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- Authors
- Li, L., He, Z.-Y., Wei, X.-W., Gao, G.-P., & Wei, Y.-Q.
- Affiliations
- Sichuan University (CN)
- Lab for Aging Research, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China
- Gene Therapy Center, University of Massachusetts Medical School, Worcester, Massachusetts.
- ORCID
- Li, Ling
- Venue
- Human Gene Therapy
- Publisher
- SAGE Publications
- Published
- 2015-07
- Volume
- 26
- Issue
- 7
- Pages
- 452-462
- ISSN
- 1043-0342 (ISSN-L)
- 1557-7422
- OpenAlex
- W1710257910
- Cited by
- 202
- References
- 134
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 16 · 2023: 16 · 2022: 18 · 2021: 25 · 2020: 24 · 2019: 28 · 2018: 22 · 2017: 15 · 2016: 18 · 2015: 3
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- 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, non-viral vectors, genome editing, lipid nanoparticles, polymer-based nanocarriers, in vivo gene delivery, clinical gene therapy
- MeSH terms
- Genetic Vectors, Humans, Viruses, Genetic Therapy, CRISPR-Cas Systems
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