Genome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors
Abstract
The development of new CRISPR-Cas genome editing tools continues to drive major advances in the life sciences. Four classes of CRISPR-Cas-derived genome editing agents-nucleases, base editors, transposases/recombinases and prime editors-are currently available for modifying genomes in experimental systems. Some of these agents have also moved rapidly into the clinic. Each tool comes with its own capabilities and limitations, and major efforts have broadened their editing capabilities, expanded their targeting scope and improved editing specificity. We analyze key considerations when choosing genome editing agents and identify opportunities for future improvements and applications in basic research and therapeutics.
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Advances in mRNA-based gene editing tools, including CRISPR-Cas9 and base editing platforms, provide an opportunity for one-and-done treatments for monogenic diseases.
“Advances in mRNA-based gene editing tools, including CRISPR-Cas9 and base editing platforms, provide an opportunity for “one-and-done” treatments for monogenic diseases (5, 6).”
From Ionizable Lipid Nanoparticles for Therapeutic Base Editing of Congenital Brain Disease (2023) · cites this paper as [6]
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Yuan, T., Yan, N., Fei, T., Zheng, J., Meng, J., Li, N., Liu, J., Zhang, H., Xie, L., Ying, W., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25217-y · Cited by 55 · see citing works
Fukushima, K., & Pollock, D. D. (2023) · Nature Ecology & Evolution · doi:10.1038/s41559-022-01932-7 · Cited by 55 · see citing works
Kondo, K., & Taguchi, C. (2022) · Food Safety · doi:10.14252/foodsafetyfscj.d-21-00016 · Cited by 49 · see citing works
Tariq, A., Mushtaq, M., Yaqoob, H., Bhat, B. A., Zargar, S. M., Raza, A., Ali, S., Charagh, S., Mubarik, M. S., Zaman, Q. U., et al. (2023) · GM Crops & Food · doi:10.1080/21645698.2023.2219111 · Cited by 45 · see citing works
Adeno-Associated Virus (AAV) - Based Gene Therapies for Retinal Diseases: Where are We?
Ail, D., Malki, H., Zin, E. A., & Dalkara, D. (2023) · The Application of Clinical Genetics · doi:10.2147/tacg.s383453 · Cited by 40 · see citing works
Xiong, X., Li, Z., Liang, J., Liu, K., Li, C., & Li, J.-F. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac166 · Cited by 41 · see citing works
Salman, A., Kantor, A., McClements, M. E., Marfany, G., Trigueros, S., & MacLaren, R. E. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14091842 · Cited by 37 · see citing works
New Approaches for Targeting PCSK9: Small-Interfering Ribonucleic Acid and Genome Editing
Oostveen, R. F., Khera, A. V., Kathiresan, S., Stroes, E. S. G., Fitzgerald, K., Harms, M. J., Oakes, B. L., & Kastelein, J. J. P. (2023) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.122.317963 · Cited by 31 · see citing works
Development of multiplexed orthogonal base editor (MOBE) systems
Cowan, Q. T., Gu, S., Gu, W., Ranzau, B. L., Simonson, T. S., & Komor, A. C. (2025) · Nature Biotechnology · doi:10.1038/s41587-024-02240-0 · Cited by 26 · see citing works
Genome Editing of Veterinary Relevant Mycoplasmas Using a CRISPR-Cas Base Editor System
Ipoutcha, T., Rideau, F., Gourgues, G., Arfi, Y., Lartigue, C., Blanchard, A., & Sirand-Pugnet, P. (2022) · Applied and Environmental Microbiology · doi:10.1128/aem.00996-22 · Cited by 19 · see citing works
CRISPR/cas-mediated genome editing in sorghum — recent progress, challenges and prospects
Parikh, A., Brant, E. J., Baloglu, M. C., & Altpeter, F. (2021) · In Vitro Cellular & Developmental Biology - Plant · doi:10.1007/s11627-021-10215-y · Cited by 18 · see citing works
Prime-editing methods and pegRNA design programs
Mikhaylova, E. V., Kuluev, B. R., Gerashchenkov, G. A., Chemeris, D. A., Garafutdinov, R. R., Kuluev, A. R., Baymiev, A. K., Baymiev, A. K., & Chemeris, A. V. (2024) · Molecular Biology · doi:10.1134/s0026893324010084 · Cited by 15 · see citing works
Development of a base editor for convenient and multiplex genome editing in cyanobacteria
Li, X.-D., Liu, L.-M., Xi, Y.-C., Sun, Q.-W., Luo, Z., Huang, H.-L., Wang, X.-W., Jiang, H.-B., & Chen, W. (2024) · Communications Biology · doi:10.1038/s42003-024-06696-3 · Cited by 14 · see citing works
CRISPRmap: Sequencing-free optical pooled screens mapping multi-omic phenotypes in cells and tissue
Gu, J., Iyer, A., Wesley, B., Taglialatela, A., Leuzzi, G., Hangai, S., Decker, A., Gu, R., Klickstein, N., Shuai, Y., et al. (2023) · doi:10.1101/2023.12.26.572587 · Cited by 10 · see citing works
- Authors
- Anzalone, A. V., Koblan, L. W., & Liu, D. R.
- Affiliations
- Broad Institute (US)
- Corresponding author
- Liu, David R.
- Venue
- Nature Biotechnology
- Published
- 2020-06-22
- Volume
- 38
- Issue
- 7
- Pages
- 824-844
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W3035764705
- Cited by
- 2,237
- References
- 51
- Citations by year
- 2026: 267 · 2025: 316 · 2024: 414 · 2023: 412 · 2022: 412 · 2021: 326 · 2020: 90
- FWCI
- 30.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases (U01AI142756)
- U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (RM1HG009490)
- U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (R01EB022376)
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (R35GM118062)
- Howard Hughes Medical Institute (Liu investigatorship)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- CRISPR/Cas genome editing, CRISPR-Cas nucleases, base editors, transposase, recombinases, prime editors, genome editing tools, editing specificity, tool selection
- MeSH terms
- Gene Editing, Endonucleases, Humans, Genome, Transposases, Recombinases, DNA Breaks, Double-Stranded, CRISPR-Cas Systems
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