Methods and Applications of CRISPR-Mediated Base Editing in Eukaryotic Genomes
Open accessAbstract
The past several years have seen an explosion in development of applications for the CRISPR-Cas9 system, from efficient genome editing, to high-throughput screening, to recruitment of a range of DNA and chromatin-modifying enzymes. While homology-directed repair (HDR) coupled with Cas9 nuclease cleavage has been used with great success to repair and re-write genomes, recently developed base-editing systems present a useful orthogonal strategy to engineer nucleotide substitutions. Base editing relies on recruitment of cytidine deaminases to introduce changes (rather than double-stranded breaks and donor templates) and offers potential improvements in efficiency while limiting damage and simplifying the delivery of editing machinery. At the same time, these systems enable novel mutagenesis strategies to introduce sequence diversity for engineering and discovery. Here, we review the different base-editing platforms, including their deaminase recruitment strategies and editing outcomes, and compare them to other CRISPR genome-editing technologies. Additionally, we discuss how these systems have been applied in therapeutic, engineering, and research settings. Lastly, we explore future directions of this emerging technology.
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Base editing does not induce a high level of double-stranded DNA breaks.
“A new-generation of genome editing tool, Base Editing (BE) system, enables precise base changes (reviewed in 4, 5), does not induce a high-level of DSBs, and finally does not require HDR donors for gene repair 4, 5.”
From Adenine base editing in an adult mouse model of tyrosinaemia (2019) · cites this paper as [4]
Base editing does not require homology-directed repair donors for gene repair.
“A new-generation of genome editing tool, Base Editing (BE) system, enables precise base changes (reviewed in 4, 5), does not induce a high-level of DSBs, and finally does not require HDR donors for gene repair 4, 5.”
From Adenine base editing in an adult mouse model of tyrosinaemia (2019) · cites this paper as [4]
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References 200 · Cited by 234
- Authors
- Hess, G. T., Tycko, J., Yao, D., & Bassik, M. C.
- Affiliations
- Stanford University (US)
- Corresponding author
- Bassik, Michael C.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2017-10
- Volume
- 68
- Issue
- 1
- Pages
- 26-43
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC5997582
- OpenAlex
- W2761894131
- Cited by
- 234
- References
- 200
- Citations by year
- 2026: 12 · 2025: 10 · 2024: 15 · 2023: 13 · 2022: 25 · 2021: 32 · 2020: 32 · 2019: 54 · 2018: 38 · 2017: 3
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 369 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH Director's New Innovator Award Program (1DP2HD084069-01)
- NIH (T32HG000044)
- National Science Foundation (NSF) Graduate Research Fellowship (DGE-1656518)
- 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 › Molecular Biology › DNA Repair Mechanisms
- Keywords
- CRISPR base editing, cytidine deaminase, CRISPR/Cas9, nucleotide substitution, genome editing, mutagenesis, homology-directed repair, eukaryotic genomes, therapeutic genome editing
- MeSH terms
- Gene Editing, RNA, Guide, CRISPR-Cas Systems, Animals, DNA Repair, Endonucleases, Eukaryotic Cells, Genetic Engineering, Humans, Nucleotides, Mutagenesis, Genome, Directed Molecular Evolution, Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR-Cas Systems
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