The DOI matches its Crossref record; 35 of the 36 references it cites were found in a registry or an index.
Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage
Open accessAbstract
Current genome-editing technologies introduce double-stranded (ds) DNA breaks at a target locus as the first step to gene correction. Although most genetic diseases arise from point mutations, current approaches to point mutation correction are inefficient and typically induce an abundance of random insertions and deletions (indels) at the target locus resulting from the cellular response to dsDNA breaks. Here we report the development of 'base editing', a new approach to genome editing that enables the direct, irreversible conversion of one target DNA base into another in a programmable manner, without requiring dsDNA backbone cleavage or a donor template. We engineered fusions of CRISPR/Cas9 and a cytidine deaminase enzyme that retain the ability to be programmed with a guide RNA, do not induce dsDNA breaks, and mediate the direct conversion of cytidine to uridine, thereby effecting a C→T (or G→A) substitution. The resulting 'base editors' convert cytidines within a window of approximately five nucleotides, and can efficiently correct a variety of point mutations relevant to human disease. In four transformed human and murine cell lines, second- and third-generation base editors that fuse uracil glycosylase inhibitor, and that use a Cas9 nickase targeting the non-edited strand, manipulate the cellular DNA repair response to favour desired base-editing outcomes, resulting in permanent correction of ~15-75% of total cellular DNA with minimal (typically ≤1%) indel formation. Base editing expands the scope and efficiency of genome editing of point mutations.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“An alternative approach is to use CRISPR-Cas9 coupled to DNA editing enzymes that catalyze targeted A-to-G or Cto-T genomic sequence changes without inducing a break in DNA, potentially reversing pathogenic single-nucleotide changes or disabling genes via the introduction of a stop codon 25,26 .”
From The promise and challenge of therapeutic genome editing (2020) · cites this paper as [25]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Base editors are one such tool, which couple Cas9 nickases with nucleotide deaminases to achieve single nucleotide conversion without introducing DSBs.”
From Off-target effects in CRISPR/Cas9 gene editing (2023) · cites this paper as Komor et al., 2016
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The discovery of spontaneous hydrolytic deamination of cytosine converting C-G base pairs to T-A in humans highlighted the potential of base editing for direct base pair conversion without requiring double-strand breaks or homology repair templates (Komor, et al., 2016).”
From Emerging applications of gene editing technologies for the development of climate-resilient crops (2025) · cites this paper as Komor, et al., 2016
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Next-generation CRISPR tools, such as base editors, use enzymes like cytidine or adenine deaminases fused to Cas9 to introduce single nucleotide variants (SNVs) without DSBs.12,13”
From Protocol to create isogenic disease models from adult stem cell-derived organoids using next-generation CRISPR tools (2024) · cites this paper as [12]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In the same paper, with enhanced third-generation base editors, Komor et al. achieved >30-fold greater editing efficiency in various human cell lines when compared to HDR-mediated Cas9 editing, with fewer indel formation.”
From CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool (2019) · cites this paper as [82]
Experimental — accuracy not yet measured
The cited source says what the claim attributes to it.
In the citing paper
“Alternatives to DNA cleavage-induced editing include using CRISPR-Cas9 for direct chemical sequence alteration (base editing) 25,26 , providing RNA templates for gene alteration (prime editing) 27,28 , and for transcriptional control (CRISPR interference, CRISPRi; CRISPR activation, CRISPRa) 29,30 (Fig. 3).”
From The promise and challenge of therapeutic genome editing (2020) · cites this paper as [25]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“CBE converts cytosine to thymine”
From Off-target effects in CRISPR/Cas9 gene editing (2023) · cites this paper as Komor et al., 2016
The cited source says what the claim attributes to it.
In the citing paper
“First-generation base editors had limitations such as low efficiency and base excision repair (BER) activity that reversed edits (Komor et al., 2016).”
From Emerging applications of gene editing technologies for the development of climate-resilient crops (2025) · cites this paper as Komor et al., 2016
The cited source says what the claim attributes to it.
In the citing paper
“Second-generation editors, such as APOBEC-XTEN-dCas9-UGI, added an uracil DNA glycosylase inhibitor (UGI) to improve C-to-T conversion (Komor et al., 2016) but still had <0.1% indel formation, limiting precision (Azameti and Dauda, 2021).”
From Emerging applications of gene editing technologies for the development of climate-resilient crops (2025) · cites this paper as Komor et al., 2016
The cited source says what the claim attributes to it.
In the citing paper
“Fusion of a cytidine deaminase (rAPOBEC1) to a partially inactive nickase-Cas9(D10A) protein results in a cytidine base editor (CBE) that allows for C > T base changes via a uracil intermediate28”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [28]
The cited source says what the claim attributes to it.
In the citing paper
“Coupling this Cas9n or dCas9, the catalytically “dead” variant of Cas9, with a cytidine deaminase enzyme enables the gRNA-mediated deamination of cytosine (C) bases in the non-target DNA strand into uracil (U), which shares the base-pairing properties of thymine (T) [82].”
From CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool (2019) · cites this paper as [82]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The second study used CRISPR-Cas9-mediated genome editing to remove a mutation in exon 23 in the mdx mouse model of DMD, providing partial recovery of functional dystrophin protein in skeletal myofibers and cardiac muscle 25,26,49 .”
From The promise and challenge of therapeutic genome editing (2020) · cites this paper as [25]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“ABE catalyzes the editing from adenine to guanine”
From Off-target effects in CRISPR/Cas9 gene editing (2023) · cites this paper as Komor et al., 2016
Experimental — accuracy not yet measuredIn the citing paper
“Variations on these methods enable the functional evaluation of genes (via knockout screens124), regulatory elements (using CRISPR interference and CRISPR activation screens125,126), and genetic variants (base editors127) at increasing scale and resolution29.”
From A brief history of human disease genetics (2020) · cites this paper as [127]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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
Multiplex Genome Engineering Using CRISPR/Cas Systems
Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., et al. (2013) · Science · doi:10.1126/science.1231143 · Cited by 15,339
Genome engineering using the CRISPR-Cas9 system
Ran, F. A., Hsu, P. D., Wright, J., Agarwala, V., Scott, D. A., & Zhang, F. (2013) · Nature Protocols · doi:10.1038/nprot.2013.143 · Cited by 11,133
Shrestha, S., & Offer, S. M. (2016) · Medical Epigenetics · doi:10.1159/000444713 · Cited by 8,951
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
ClinVar: public archive of interpretations of clinically relevant variants
Landrum, M. J., Lee, J. M., Benson, M., Brown, G., Chao, C., Chitipiralla, S., Gu, B., Hart, J., Hoffman, D., Hoover, J., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1222 · Cited by 2,758
High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects
Kleinstiver, B. P., Pattanayak, V., Prew, M. S., Tsai, S. Q., Nguyen, N. T., Zheng, Z., & Joung, J. K. (2016) · Nature · doi:10.1038/nature16526 · Cited by 2,673
Rationally engineered Cas9 nucleases with improved specificity
Slaymaker, I. M., Gao, L., Zetsche, B., Scott, D. A., Yan, W. X., & Zhang, F. (2016) · Science · doi:10.1126/science.aad5227 · Cited by 2,414
GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases
Tsai, S. Q., Zheng, Z., Nguyen, N. T., Liebers, M., Topkar, V. V., Thapar, V., Wyvekens, N., Khayter, C., Iafrate, A. J., Le, L. P., et al. (2015) · Nature Biotechnology · doi:10.1038/nbt.3117 · Cited by 2,268
Mali, P., Aach, J., Stranges, P. B., Esvelt, K. M., Moosburner, M., Kosuri, S., Yang, L., & Church, G. M. (2013) · Nature Biotechnology · doi:10.1038/nbt.2675 · Cited by 1,752
Cited by
Sorted by citations
Search-and-replace genome editing without double-strand breaks or donor DNA
Anzalone, A. V., Randolph, P. B., Davis, J. R., Sousa, A. A., Koblan, L. W., Levy, J. M., Chen, P. J., Wilson, C., Newby, G. A., Raguram, A., et al. (2019) · Nature · doi:10.1038/s41586-019-1711-4 · Cited by 4,767
Self-citationProgrammable base editing of A•T to G•C in genomic DNA without DNA cleavage
Gaudelli, N. M., Komor, A. C., Rees, H. A., Packer, M. S., Badran, A. H., Bryson, D. I., & Liu, D. R. (2017) · Nature · doi:10.1038/nature24644 · Cited by 4,184
Self-citationGenome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors
Anzalone, A. V., Koblan, L. W., & Liu, D. R. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0561-9 · Cited by 2,237
Self-citationEfficient generation of mouse models of human diseases via ABE- and BE-mediated base editing
Liu, Z., Lu, Z., Yang, G., Huang, S., Li, G., Feng, S., Liu, Y., Li, J., Yu, W., Zhang, Y., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04768-7 · Cited by 2,103
Kosicki, M., Tomberg, K., & Bradley, A. (2018) · Nature Biotechnology · doi:10.1038/nbt.4192 · Cited by 1,883
Cox, D. B. T., Gootenberg, J. S., Abudayyeh, O. O., Franklin, B., Kellner, M. J., Joung, J., & Zhang, F. (2017) · Science · doi:10.1126/science.aaq0180 · Cited by 1,834
Base editing: precision chemistry on the genome and transcriptome of living cells
Rees, H. A., & Liu, D. R. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0059-1 · Cited by 1,675
Self-citationCRISPR/Cas Genome Editing and Precision Plant Breeding in Agriculture
Chen, K., Wang, Y., Zhang, R., Zhang, H., & Gao, C. (2019) · Annual Review of Plant Biology · doi:10.1146/annurev-arplant-050718-100049 · Cited by 1,696
The CRISPR tool kit for genome editing and beyond
Adli, M. (2018) · Nature Communications · doi:10.1038/s41467-018-04252-2 · Cited by 1,545
CRISPResso2 provides accurate and rapid genome editing sequence analysis
Clement, K., Rees, H. A., Canver, M. C., Gehrke, J. M., Farouni, R., Hsu, J. Y., Cole, M. A., Liu, D. R., Joung, J. K., Bauer, D. E., et al. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0032-3 · Cited by 1,656
Self-citationEvolved Cas9 variants with broad PAM compatibility and high DNA specificity
Hu, J. H., Miller, S. M., Geurts, M. H., Tang, W., Chen, L., Sun, N., Zeina, C. M., Gao, X., Rees, H. A., Lin, Z., et al. (2018) · Nature · doi:10.1038/nature26155 · Cited by 1,552
Self-citationInduced pluripotent stem cell technology: a decade of progress.
Shi, Y., Inoue, H., Wu, J. C., & Yamanaka, S. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.245 · Cited by 1,525
The next generation of CRISPR–Cas technologies and applications
Pickar-Oliver, A., & Gersbach, C. A. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0131-5 · Cited by 1,459
Endogenous DNA damage as a source of genomic instability in cancer
Tubbs, A., & Nussenzweig, A. (2017) · Cell · doi:10.1016/j.cell.2017.01.002 · Cited by 1,452
CRISPR-Cas guides the future of genetic engineering
Knott, G. J., & Doudna, J. A. (2018) · Science · doi:10.1126/science.aat5011 · Cited by 1,410
Dunbar, C. E., High, K. A., Joung, J. K., Kohn, D. B., Ozawa, K., & Sadelain, M. (2018) · Science · doi:10.1126/science.aan4672 · Cited by 1,410
Targeted nucleotide editing using hybrid prokaryotic and vertebrate adaptive immune systems
Nishida, K., Arazoe, T., Yachie, N., Banno, S., Kakimoto, M., Tabata, M., Mochizuki, M., Miyabe, A., Araki, M., Hara, K. Y., et al. (2016) · Science · doi:10.1126/science.aaf8729 · Cited by 1,349
Unconstrained genome targeting with near-PAMless engineered CRISPR-Cas9 variants
Walton, R. T., Christie, K. A., Whittaker, M. N., & Kleinstiver, B. P. (2020) · Science · doi:10.1126/science.aba8853 · Cited by 1,233
Adamson, B., Norman, T. M., Jost, M., Cho, M. Y., Nuñez, J. K., Chen, Y., Villalta, J. E., Gilbert, L. A., Horlbeck, M. A., Hein, M. Y., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.048 · Cited by 1,193
Exploring treatment options in cancer: tumor treatment strategies
Liu, B., Zhou, H., Tan, L., Siu, K. T. H., & Guan, X.-Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01856-7 · Cited by 1,201
The promise and challenge of therapeutic genome editing
Doudna, J. A. (2020) · Nature · doi:10.1038/s41586-020-1978-5 · Cited by 1,126
Engineered CRISPR-Cas9 nuclease with expanded targeting space
Nishimasu, H., Shi, X., Ishiguro, S., Gao, L., Hirano, S., Okazaki, S., Noda, T., Abudayyeh, O. O., Gootenberg, J. S., Mori, H., et al. (2018) · Science · doi:10.1126/science.aas9129 · Cited by 1,100
CRISPR technology: A decade of genome editing is only the beginning
Wang, J. Y., & Doudna, J. A. (2023) · Science · doi:10.1126/science.add8643 · Cited by 1,105
Genome engineering for crop improvement and future agriculture
Gao, C. (2021) · Cell · doi:10.1016/j.cell.2021.01.005 · Cited by 1,070
Richter, M. F., Zhao, K. T., Eton, E., Lapinaite, A., Newby, G. A., Thuronyi, B. W., Wilson, C., Koblan, L. W., Zeng, J., Bauer, D. E., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0453-z · Cited by 1,020
Self-citationCRISPR-Based Technologies for the Manipulation of Eukaryotic Genomes
Komor, A. C., Badran, A. H., & Liu, D. R. (2016) · Cell · doi:10.1016/j.cell.2016.10.044 · Cited by 1,037
Self-citationRestoring synovial homeostasis in rheumatoid arthritis by targeting fibroblast-like synoviocytes
Nygaard, G., & Firestein, G. S. (2020) · Nature Reviews Rheumatology · doi:10.1038/s41584-020-0413-5 · Cited by 970
Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction
Koblan, L. W., Doman, J. L., Wilson, C., Levy, J. M., Tay, T., Newby, G. A., Maianti, J. P., Raguram, A., & Liu, D. R. (2018) · Nature Biotechnology · doi:10.1038/nbt.4172 · Cited by 944
Self-citationHorlbeck, M. A., Gilbert, L. A., Villalta, J. E., Adamson, B., Pak, R. A., Chen, Y., Fields, A. P., Park, C. Y., Corn, J. E., Kampmann, M., et al. (2016) · eLife · doi:10.7554/elife.19760 · Cited by 894
Precise base editing in rice, wheat and maize with a Cas9-cytidine deaminase fusion
Zong, Y., Wang, Y., Li, C., Zhang, R., Chen, K., Ran, Y., Qiu, J., Wang, D., & Gao, C. (2017) · Nature Biotechnology · doi:10.1038/nbt.3811 · Cited by 896
Prime genome editing in rice and wheat
Lin, Q., Zong, Y., Xue, C., Wang, S., Jin, S., Zhu, Z., Wang, Y., Anzalone, A. V., Raguram, A., Doman, J. L., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0455-x · Cited by 873
Self-citationApplications of CRISPR–Cas in agriculture and plant biotechnology
Zhu, H., Li, C., & Gao, C. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00288-9 · Cited by 870
Targeted base editing in rice and tomato using a CRISPR-Cas9 cytidine deaminase fusion
Shimatani, Z., Kashojiya, S., Takayama, M., Terada, R., Arazoe, T., Ishii, H., Teramura, H., Yamamoto, T., Komatsu, H., Miura, K., et al. (2017) · Nature Biotechnology · doi:10.1038/nbt.3833 · Cited by 812
In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates
Musunuru, K., Chadwick, A. C., Mizoguchi, T., Garcia, S. P., DeNizio, J. E., Reiss, C. W., Wang, K., Iyer, S., Dutta, C., Clendaniel, V., et al. (2021) · Nature · doi:10.1038/s41586-021-03534-y · Cited by 793
Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos
Zuo, E., Sun, Y., Wei, W., Yuan, T., Ying, W., Sun, H., Yuan, L., Steinmetz, L. M., Li, Y., & Yang, H. (2019) · Science · doi:10.1126/science.aav9973 · Cited by 782
CRISPR/Cas9 therapeutics: progress and prospects
Li, T., Yang, Y., Qi, H., Cui, W., Zhang, L., Fu, X., He, X., Liu, M., Li, P., & Yu, T. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01309-7 · Cited by 824
Komor, A. C., Zhao, K. T., Packer, M. S., Gaudelli, N. M., Waterbury, A. L., Koblan, L. W., Kim, Y. B., Badran, A. H., & Liu, D. R. (2017) · Science Advances · doi:10.1126/sciadv.aao4774 · Cited by 783
Self-citationKim, Y. B., Komor, A. C., Levy, J. M., Packer, M. S., Zhao, K. T., & Liu, D. R. (2017) · Nature Biotechnology · doi:10.1038/nbt.3803 · Cited by 758
Self-citationDrugging p53 in cancer: one protein, many targets
Hassin, O., & Oren, M. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00571-8 · Cited by 771
A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing
Mok, B. Y., de Moraes, M. H., Zeng, J., Bosch, D. E., Kotrys, A. V., Raguram, A., Hsu, F., Radey, M. C., Peterson, S. B., Mootha, V. K., et al. (2020) · Nature · doi:10.1038/s41586-020-2477-4 · Cited by 758
Self-citationEngineered pegRNAs improve prime editing efficiency
Nelson, J. W., Randolph, P. B., Shen, S. P., Everette, K. A., Chen, P. J., Anzalone, A. V., An, M., Newby, G. A., Chen, J. C., Hsu, A., et al. (2022) · Nature Biotechnology · doi:10.1038/s41587-021-01039-7 · Cited by 727
Self-citationA brief history of human disease genetics
Claussnitzer, M., Cho, J. H., Collins, R., Cox, N. J., Dermitzakis, E. T., Hurles, M. E., Kathiresan, S., Kenny, E. E., Lindgren, C. M., MacArthur, D. G., et al. (2020) · Nature · doi:10.1038/s41586-019-1879-7 · Cited by 697
RNA-guided DNA insertion with CRISPR-associated transposases
Strecker, J., Ladha, A., Gardner, Z., Schmid-Burgk, J. L., Makarova, K. S., Koonin, E. V., & Zhang, F. (2019) · Science · doi:10.1126/science.aax9181 · Cited by 707
Kleinstiver, B. P., Sousa, A. A., Walton, R. T., Tak, Y. E., Hsu, J. Y., Clement, K., Welch, M. M., Horng, J. E., Malagon-Lopez, J., Scarfò, I., et al. (2019) · Nature Biotechnology · doi:10.1038/s41587-018-0011-0 · Cited by 698
Engineered Virus-like Particles for Efficient in Vivo Delivery of Therapeutic Proteins
Banskota, S., Raguram, A., Suh, S., Du, S. W., Davis, J. R., Choi, E. H., Wang, X., Nielsen, S. C., Newby, G. A., Randolph, P. B., et al. (2022) · Cell · doi:10.1016/j.cell.2021.12.021 · Cited by 668
Self-citationCytosine, but not adenine, base editors induce genome-wide off-target mutations in rice
Jin, S., Zong, Y., Gao, Q., Zhu, Z., Wang, Y., Qin, P., Liang, C., Wang, D., Qiu, J.-L., Zhang, F., et al. (2019) · Science · doi:10.1126/science.aaw7166 · Cited by 665
Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors
Grünewald, J., Zhou, R., Garcia, S. P., Iyer, S., Lareau, C. A., Aryee, M. J., & Joung, J. K. (2019) · Nature · doi:10.1038/s41586-019-1161-z · Cited by 663
Off-target effects in CRISPR/Cas9 gene editing
Guo, C., Ma, X., Gao, F., & Guo, Y. (2023) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2023.1143157 · Cited by 704
“ABE catalyzes the editing from adenine to guanine and CBE converts cytosine to thymine (Komor et al., 2016; Gaudelli et al., 2017; Wu et al., 2022).”
BackgroundPrime editing for precise and highly versatile genome manipulation
Chen, P. J., & Liu, D. R. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00541-1 · Cited by 644
Self-citationAnzalone, A. V., Gao, X. D., Podracky, C. J., Nelson, A. T., Koblan, L. W., Raguram, A., Levy, J. M., Mercer, J. A. M., & Liu, D. R. (2022) · Nature Biotechnology · doi:10.1038/s41587-021-01133-w · Cited by 613
Self-citationPast, present, and future of CRISPR genome editing technologies
Pacesa, M., Pelea, O., & Jinek, M. (2024) · Cell · doi:10.1016/j.cell.2024.01.042 · Cited by 609
Chromothripsis as an on-target consequence of CRISPR–Cas9 genome editing
Leibowitz, M. L., Papathanasiou, S., Doerfler, P. A., Blaine, L. J., Sun, L., Yao, Y., Zhang, C.-Z., Weiss, M. J., & Pellman, D. (2021) · Nature Genetics · doi:10.1038/s41588-021-00838-7 · Cited by 583
CRISPR C-to-G base editors for inducing targeted DNA transversions in human cells
Kurt, I. C., Zhou, R., Iyer, S., Garcia, S. P., Miller, B. R., Langner, L. M., Grünewald, J., & Joung, J. K. (2021) · Nature Biotechnology · doi:10.1038/s41587-020-0609-x · Cited by 573
Predictable and precise template-free CRISPR editing of pathogenic variants
Shen, M. W., Arbab, M., Hsu, J. Y., Worstell, D., Culbertson, S. J., Krabbe, O., Cassa, C. A., Liu, D. R., Gifford, D. K., & Sherwood, R. I. (2018) · Nature · doi:10.1038/s41586-018-0686-x · Cited by 569
Self-citationEditR: A Method to Quantify Base Editing from Sanger Sequencing
Kluesner, M. G., Nedveck, D. A., Lahr, W. S., Garbe, J. R., Abrahante, J. E., Webber, B. R., & Moriarity, B. S. (2018) · The CRISPR Journal · doi:10.1089/crispr.2018.0014 · Cited by 565
Microbiome and Human Health: Current Understanding, Engineering, and Enabling Technologies
Aggarwal, N., Kitano, S., Puah, G. R. Y., Kittelmann, S., Hwang, I. Y., & Chang, M. W. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.2c00431 · Cited by 571
Therapeutic in vivo delivery of gene editing agents
Raguram, A., Banskota, S., & Liu, D. R. (2022) · Cell · doi:10.1016/j.cell.2022.03.045 · Cited by 552
Self-citationDirected evolution of CRISPR-Cas9 to increase its specificity
Lee, J. K., Jeong, E., Lee, J., Jung, M., Shin, E., Kim, Y.-H., Lee, K., Jung, I., Kim, D., Kim, S., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05477-x · Cited by 525
Self-citationDirected evolution of adenine base editors with increased activity and therapeutic application
Gaudelli, N. M., Lam, D. K., Rees, H. A., Solá-Esteves, N. M., Barrera, L. A., Born, D. A., Edwards, A., Gehrke, J. M., Lee, S., Liquori, A., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0491-6 · Cited by 533
Self-citationAlternative splicing and cancer: a systematic review
Zhang, Y., Qian, J., Gu, C., & Yang, Y. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00486-7 · Cited by 540
Expanded base editing in rice and wheat using a Cas9-adenosine deaminase fusion
Li, C., Zong, Y., Wang, Y., Jin, S., Zhang, D., Song, Q., Zhang, R., & Gao, C. (2018) · Genome biology · doi:10.1186/s13059-018-1443-z · Cited by 507
DART-seq: an antibody-free method for global m6A detection
Meyer, K. D. (2019) · Nature Methods · doi:10.1038/s41592-019-0570-0 · Cited by 490
CRISPR-Cas9 DNA Base-Editing and Prime-Editing
Kantor, A., McClements, M., & MacLaren, R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176240 · Cited by 462
Yarnall, M. T. N., Ioannidi, E. I., Schmitt-Ulms, C., Krajeski, R. N., Lim, J., Villiger, L., Zhou, W., Jiang, K., Garushyants, S. K., Roberts, N., et al. (2022) · Nature Biotechnology · doi:10.1038/s41587-022-01527-4 · Cited by 520
Off-target RNA mutation induced by DNA base editing and its elimination by mutagenesis
Zhou, C., Sun, Y., Yan, R., Liu, Y., Zuo, E., Gu, C., Han, L., Wei, Y., Hu, X., Zeng, R., et al. (2019) · Nature · doi:10.1038/s41586-019-1314-0 · Cited by 482
In vivo base editing rescues Hutchinson–Gilford progeria syndrome in mice
Koblan, L. W., Erdos, M. R., Wilson, C., Cabral, W. A., Levy, J. M., Xiong, Z., Tavarez, U. L., Davison, L. M., Gete, Y. G., Mao, X., et al. (2021) · Nature · doi:10.1038/s41586-020-03086-7 · Cited by 489
Self-citationCurrent applications and future perspective of CRISPR/Cas9 gene editing in cancer
Wang, S.-W., Gao, C., Zheng, Y.-M., Yi, L., Lu, J.-C., Huang, X.-Y., Cai, J.-B., Zhang, P.-F., Cui, Y.-H., & Ke, A.-W. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01518-8 · Cited by 478
Base editing: advances and therapeutic opportunities
Porto, E. M., Komor, A. C., Slaymaker, I. M., & Yeo, G. W.-M. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0084-6 · Cited by 499
Self-citationEntering the Modern Era of Gene Therapy
Anguela, X. M., & High, K. A. (2018) · Annual Review of Medicine · doi:10.1146/annurev-med-012017-043332 · Cited by 494
Evaluation and minimization of Cas9-independent off-target DNA editing by cytosine base editors
Doman, J. L., Raguram, A., Newby, G. A., & Liu, D. R. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0414-6 · Cited by 473
Self-citationLevy, J. M., Yeh, W.-H., Pendse, N. D., Davis, J. R., Hennessey, E., Butcher, R. M., Koblan, L. W., Comander, J., Liu, Q., & Liu, D. R. (2020) · Nature Biomedical Engineering · doi:10.1038/s41551-019-0501-5 · Cited by 476
Self-citationSynthetic lethality as an engine for cancer drug target discovery
Huang, A., Garraway, L. A., Ashworth, A., & Weber, B. L. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0046-z · Cited by 490
Directed evolution using dCas9-targeted somatic hypermutation in mammalian cells
Hess, G. T., Frésard, L., Han, K., Lee, C. H., Li, A., Cimprich, K. A., Montgomery, S. B., & Bassik, M. C. (2016) · Nature Methods · doi:10.1038/nmeth.4038 · Cited by 474
Current Challenges of iPSC-Based Disease Modeling and Therapeutic Implications
Doss, M. X., & Sachinidis, A. (2019) · Cells · doi:10.3390/cells8050403 · Cited by 486
Glycosylase base editors enable C-to-A and C-to-G base changes
Zhao, D., Li, J., Li, S., Xin, X., Hu, M., Price, M. A., Rosser, S. J., Bi, C., & Zhang, X. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0592-2 · Cited by 468
Latest Developed Strategies to Minimize the Off-Target Effects in CRISPR-Cas-Mediated Genome Editing
Naeem, M., Majeed, S., Hoque, M. Z., & Ahmad, I. (2020) · Cells · doi:10.3390/cells9071608 · Cited by 457
A cytosine deaminase for programmable single-base RNA editing
Abudayyeh, O. O., Gootenberg, J. S., Franklin, B., Koob, J. G., Kellner, M. J., Ladha, A., Joung, J., Kirchgatterer, P. C., Cox, D. B. T., & Zhang, F. (2019) · Science · doi:10.1126/science.aax7063 · Cited by 460
Am I ready for CRISPR? A user's guide to genetic screens
Doench, J. G. (2018) · Nature Reviews Genetics · doi:10.1038/nrg.2017.97 · Cited by 452
Applications and potential of genome editing in crop improvement
Zhang, Y., Massel, K., Godwin, I. D., & Gao, C. (2018) · Genome biology · doi:10.1186/s13059-018-1586-y · Cited by 459
Engineering the next generation of cell-based therapeutics
Bashor, C. J., Hilton, I. B., Bandukwala, H. S., Smith, D. M., & Omid Veiseh, A. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00476-6 · Cited by 472
Cornerstones of CRISPR–Cas in drug discovery and therapy
Fellmann, C., Gowen, B. G., Lin, P., Doudna, J. A., & Corn, J. E. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.238 · Cited by 452
Adenine base editing in mouse embryos and an adult mouse model of Duchenne muscular dystrophy
Ryu, S.-M., Koo, T., Kim, K., Lim, K., Baek, G., Kim, S., Kim, H. S., Kim, D.-E., Lee, H., Chung, E., et al. (2018) · Nature Biotechnology · doi:10.1038/nbt.4148 · Cited by 452
CRISPR in cancer biology and therapy
Katti, A., Diaz, B. J., Caragine, C. M., Sanjana, N. E., & Dow, L. E. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00441-w · Cited by 457
Progress and prospects in plant genome editing
Yin, K., Gao, C., & Qiu, J. (2017) · Nature Plants · doi:10.1038/nplants.2017.107 · Cited by 445
An APOBEC3A-Cas9 base editor with minimized bystander and off-target activities
Gehrke, J. M., Cervantes, O., Clement, K., Wu, Y., Zeng, J., Bauer, D. E., Pinello, L., & Joung, J. K. (2018) · Nature Biotechnology · doi:10.1038/nbt.4199 · Cited by 439
Efficient C-to-T base editing in plants using a fusion of nCas9 and human APOBEC3A
Zong, Y., Song, Q., Li, C., Jin, S., Zhang, D., Wang, Y., Qiu, J., & Gao, C. (2018) · Nature Biotechnology · doi:10.1038/nbt.4261 · Cited by 440
PnB Designer: a web application to design prime and base editor guide RNAs for animals and plants
Siegner, S. M., Karasu, M. E., Schröder, M., Kontarakis, Z., & Corn, J. E. (2021) · BMC Bioinformatics · doi:10.1186/s12859-021-04034-6 · Cited by 436
Base editing with a Cpf1–cytidine deaminase fusion
Li, X., Wang, Y., Liu, Y., Yang, B., Wang, X., Wei, J., Lu, Z., Zhang, Y., Wu, J., Huang, X., et al. (2018) · Nature Biotechnology · doi:10.1038/nbt.4102 · Cited by 426
Treatment of a metabolic liver disease by in vivo genome base editing in adult mice
Villiger, L., Grisch‐Chan, H. M., Lindsay, H. A., Ringnalda, F. C. A. S., Pogliano, C. B., Allegri, G., Fingerhut, R., Häberle, J., Matos, J., Robinson, M. D., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0209-1 · Cited by 426
Genome-Editing Technologies: Principles and Applications
Gaj, T., Sirk, S. J., Shui, S.-L., & Liu, J. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a023754 · Cited by 381
Xu, Y., & Li, Z. (2020) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2020.08.031 · Cited by 457
Precise Editing of a Target Base in the Rice Genome Using a Modified CRISPR/Cas9 System
Lu, Y., & Zhu, J. (2016) · Molecular Plant · doi:10.1016/j.molp.2016.11.013 · Cited by 423
Rees, H. A., Komor, A. C., Yeh, W.-H., Caetano-Lopes, J., Warman, M., Edge, A. S. B., & Liu, D. R. (2017) · Nature Communications · doi:10.1038/ncomms15790 · Cited by 412
Self-citationTargeted AID-mediated mutagenesis (TAM) enables efficient genomic diversification in mammalian cells
Ma, Y., Zhang, J., Yin, W., Zhang, Z., Song, Y., & Chang, X. (2016) · Nature Methods · doi:10.1038/nmeth.4027 · Cited by 419
Engineered miniature CRISPR-Cas system for mammalian genome regulation and editing
Xu, X., Chemparathy, A. G., Zeng, L., Kempton, H. R., Shang, S., Nakamura, M., & Qi, L. S. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.08.008 · Cited by 411
Targeted, random mutagenesis of plant genes with dual cytosine and adenine base editors
Li, C., Zhang, R., Meng, X., Chen, S., Zong, Y., Lu, C., Qiu, J., Chen, Y., Li, J., & Gao, C. (2020) · Nature Biotechnology · doi:10.1038/s41587-019-0393-7 · Cited by 410
The CRISPR-Cas toolbox and gene editing technologies
Liu, G., Lin, Q., Jin, S., & Gao, C. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.12.002 · Cited by 422
Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease
Musunuru, K., Grandinette, S. A., Wang, X., Hudson, T. R., Briseno, K., Berry, A. M., Hacker, J. L., Hsu, A., Silverstein, R. A., Hille, L. T., et al. (2025) · New England Journal of Medicine · doi:10.1056/nejmoa2504747 · Cited by 409
Self-citationApoE4: an emerging therapeutic target for Alzheimer’s disease
Safieh, M., Korczyn, A. D., & Michaelson, D. M. (2019) · BMC Medicine · doi:10.1186/s12916-019-1299-4 · Cited by 449
Advances in genome editing through control of DNA repair pathways
Yeh, C. D., Richardson, C. D., & Corn, J. E. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0425-z · Cited by 425
Metadata
- Authors
- Komor, A. C., Kim, Y. B., Packer, M. S., Zuris, J. A., & Liu, D. R.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Liu, David R.
- Venue
- Nature
- Published
- 2016-04-20
- Volume
- 533
- Issue
- 7603
- Pages
- 420-424
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4873371
- OpenAlex
- W2336828812
- Cited by
- 5,437
- References
- 36
- Citations by year
- 2026: 564 · 2025: 660 · 2024: 664 · 2023: 719 · 2022: 681 · 2021: 614 · 2020: 540 · 2019: 408 · 2018: 338 · 2017: 182 · 2016: 61
- FWCI
- 171.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of General Medical Sciences (T32GM008313, F32 GM 106601-2, F32GM106601, F32 GM 112366-2, R01GM065400, F32GM112366)
- National Institute of Biomedical Imaging and Bioengineering (R01EB022376)
- 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
- base editing, CRISPR/Cas9, cytidine deaminase, point mutation correction, Cas9 nickase, DNA repair, guide RNA, genome editing, human disease models
- MeSH terms
- APOBEC-1 Deaminase, RNA, Guide, CRISPR-Cas Systems, Animals, Base Sequence, Cell Line, Cytidine, Cytidine Deaminase, Deoxyribonuclease I, DNA, DNA Repair, Genetic Engineering, Humans, Templates, Genetic, Uridine, Genes, p53, Genome, Point Mutation, Mice, Uracil-DNA Glycosidase, Apolipoprotein E4, DNA Cleavage, INDEL Mutation, Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR-Cas Systems, CRISPR-Associated Proteins
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
