Cited by 671CRISPR and Genetic EngineeringRNA regulation and diseaseRNA Interference and Gene Delivery

The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.

Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors

Open access

Grünewald, Julian, Zhou, Ronghao, Garcia, Sara P., Iyer, Sowmya, Lareau, Caleb A., Aryee, Martin J., Joung, J. Keith·2019·Nature

DOI 10.1038/s41586-019-1161-zPMC PMC6657343

Open this paper in CoChat — free account

Abstract

CRISPR-Cas base-editor technology enables targeted nucleotide alterations, and is being increasingly used for research and potential therapeutic applications 1,2. The most widely used cytosine base editors (CBEs) induce deamination of DNA cytosines using the rat APOBEC1 enzyme, which is targeted by a linked Cas protein-guide RNA complex 3,4. Previous studies of the specificity of CBEs have identified off-target DNA edits in mammalian cells 5,6. Here we show that a CBE with rat APOBEC1 can cause extensive transcriptome-wide deamination of RNA cytosines in human cells, inducing tens of thousands of C-to-U edits with frequencies ranging from 0.07% to 100% in 38-58% of expressed genes. CBE-induced RNA edits occur in both protein-coding and non-protein-coding sequences and generate missense, nonsense, splice site, and 5' and 3' untranslated region mutations. We engineered two CBE variants bearing mutations in rat APOBEC1 that substantially decreased the number of RNA edits (by more than 390-fold and more than 3,800-fold) in human cells. These variants also showed more precise on-target DNA editing than the wild-type CBE and, for most guide RNAs tested, no substantial reduction in editing efficiency. Finally, we show that an adenine base editor 7 can also induce transcriptome-wide RNA edits. These results have implications for the use of base editors in both research and clinical settings, illustrate the feasibility of engineering improved variants with reduced RNA editing activities, and suggest the need to more fully define and characterize the RNA off-target effects of deaminase enzymes in base editor platforms.

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

Crossref · 10.1038/s41586-019-1161-z

Cites

37 of 37 references verified0 citation errors · 0 not checkable

Statistics

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709
The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data
McKenna, A., Hanna, M., Banks, E., Sivachenko, A., Cibulskis, K., Kernytsky, A., Garimella, K., Altshuler, D., Gabriel, S., Daly, M., et al. (2010) · Genome Research · doi:10.1101/gr.107524.110 · Cited by 27,895
WebLogo: A Sequence Logo Generator: Figure 1Preprint
Crooks, G. E., Hon, G. C., Chandonia, J., & Brenner, S. E. (2004) · Genome Research · doi:10.1101/gr.849004 · Cited by 12,418
A framework for variation discovery and genotyping using next-generation DNA sequencing data
DePristo, M. A., Banks, E., Poplin, R. E., Garimella, K. V., Maguire, J., Hartl, C., Philippakis, A., del Angel, G., Rivas, M. A., Hanna, M., et al. (2011) · Nature Genetics · doi:10.1038/ng.806 · Cited by 11,457
Enzymatic assembly of DNA molecules up to several hundred kilobases
Gibson, D. G., Young, L., Chuang, R.-Y., Venter, J. C., Hutchison, C. A., & Smith, H. O. (2009) · Nature Methods · doi:10.1038/nmeth.1318 · Cited by 10,088
The Phyre2 web portal for protein modeling, prediction and analysis
Kelley, L. A., Mezulis, S., Yates, C. M., Wass, M. N., & Sternberg, M. J. E. (2015) · Nature Protocols · doi:10.1038/nprot.2015.053 · Cited by 9,652
The Ensembl Variant Effect Predictor
McLaren, W., Gil, L., Hunt, S. E., Riat, H. S., Ritchie, G. R. S., Thormann, A., Flicek, P., & Cunningham, F. (2016) · Genome Biology · doi:10.1186/s13059-016-0974-4 · Cited by 8,099
Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage
Komor, A. C., Kim, Y. B., Packer, M. S., Zuris, J. A., & Liu, D. R. (2016) · Nature · doi:10.1038/nature17946 · Cited by 5,437
Programmable 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

Show all 37 references

Sorted by citations

Genome 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
The promise and challenge of therapeutic genome editing
Doudna, J. A. (2020) · Nature · doi:10.1038/s41586-020-1978-5 · Cited by 1,126
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
Phage-assisted evolution of an adenine base editor with improved Cas domain compatibility and activity
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
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
Self-citation
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
“The RNA off-target effects can be detected by RNA-seq (Grünewald et al., 2019; Zhou et al., 2019) and are believed to be transient given the short lifetime of RNA.”
Background
Lineage tracing meets single-cell omics: opportunities and challenges
Wagner, D. E., & Klein, A. M. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-020-0223-2 · Cited by 617
Prime 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
High-content CRISPR screening
Bock, C., Datlinger, P., Chardon, F. M., Coelho, M. A., Dong, M. B., Lawson, K. A., Lu, T., Maroc, L., Norman, T. M., Song, B., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-021-00093-4 · Cited by 626
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
Self-citation
Directed 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
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
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
Current 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
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
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
Self-citation
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
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
The emerging and uncultivated potential of CRISPR technology in plant science
Zhang, Y., Malzahn, A. A., Sretenovic, S., & Qi, Y. (2019) · Nature Plants · doi:10.1038/s41477-019-0461-5 · Cited by 414
CRISPR/Cas Systems in Genome Editing: Methodologies and Tools for sgRNA Design, Off‐Target Evaluation, and Strategies to Mitigate Off‐Target Effects
Manghwar, H., Li, B., Ding, X., Hussain, A., Lindsey, K., Zhang, X., & Jin, S. (2020) · Advanced Science · doi:10.1002/advs.201902312 · Cited by 347
In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels
Rothgangl, T., Dennis, M. K., Lin, P. J. C., Oka, R., Witzigmann, D., Villiger, L., Qi, W., Hruzova, M., Kissling, L., Lenggenhager, D., et al. (2021) · Nature Biotechnology · doi:10.1038/s41587-021-00933-4 · Cited by 378
CRISPR DNA base editors with reduced RNA off-target and self-editing activities
Grünewald, J., Zhou, R., Iyer, S., Lareau, C. A., Garcia, S. P., Aryee, M. J., & Joung, J. K. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0236-6 · Cited by 332
Self-citation
Therapeutic base editing of human hematopoietic stem cells
Zeng, J., Wu, Y., Ren, C., Bonanno, J., Shen, A. H., Shea, D. N., Gehrke, J. M., Clement, K., Luk, K., Yao, Q., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0790-y · Cited by 281
Self-citation
Programmable RNA editing by recruiting endogenous ADAR using engineered RNAs
Qu, L., Yi, Z., Zhu, S., Wang, C., Cao, Z., Zhou, Z. L., Yuan, P., Yu, Y. F., Tian, F., Liu, Z., et al. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0178-z · Cited by 292
Evolution of an adenine base editor into a small, efficient cytosine base editor with low off-target activity
Neugebauer, M. E., Hsu, A., Arbab, M., Krasnow, N. A., McElroy, A. N., Pandey, S., Doman, J. L., Huang, T. P., Raguram, A., Banskota, S., et al. (2022) · Nature Biotechnology · doi:10.1038/s41587-022-01533-6 · Cited by 282
Precision genome editing in plants: state-of-the-art in CRISPR/Cas9-based genome engineering
Wada, N., Ueta, R., Osakabe, Y., & Osakabe, K. (2020) · BMC Plant Biology · doi:10.1186/s12870-020-02385-5 · Cited by 279
CRISPR technologies for genome, epigenome and transcriptome editing
Villiger, L., Joung, J., Koblan, L. W., Weissman, J. S., Abudayyeh, O. O., & Gootenberg, J. S. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00697-6 · Cited by 280
Self-citation
High-content CRISPR screening
Bock, C., Datlinger, P., Chardon, F. M., Coelho, M. A., Dong, M. B., Lawson, K. A., Lu, T., Maroc, L., Norman, T. M., Song, B., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-022-00098-7 · Cited by 258
Functions and consequences of AID/APOBEC-mediated DNA and RNA deamination
Pecori, R., Giorgio, S. D., Lorenzo, J. P., & Papavasiliou, F. N. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00459-8 · Cited by 262
Precise correction of Duchenne muscular dystrophy exon deletion mutations by base and prime editing
Chemello, F., Chai, A. C., Li, H. Z., Rodríguez-Caycedo, C., Sanchez‐Ortiz, E., Atmanli, A., Mireault, A. A., Liu, N., Bassel‐Duby, R., & Olson, E. N. (2021) · Science Advances · doi:10.1126/sciadv.abg4910 · Cited by 255
A dual-deaminase CRISPR base editor enables concurrent adenine and cytosine editing
Grünewald, J., Zhou, R., Lareau, C. A., Garcia, S. P., Iyer, S., Miller, B. R., Langner, L. M., Hsu, J. Y., Aryee, M. J., & Joung, J. K. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0535-y · Cited by 242
Self-citation
Genome editing with the CRISPR‐Cas system: an art, ethics and global regulatory perspective
Zhang, D., Hussain, A., Manghwar, H., Xie, K., Xie, S., Zhao, S., Larkin, R. M., Qing, P., Jin, S., & Ding, F. (2020) · Plant Biotechnology Journal · doi:10.1111/pbi.13383 · Cited by 254
Highly efficient multiplex human T cell engineering without double-strand breaks using Cas9 base editors
Webber, B. R., Lonetree, C.-L., Kluesner, M. G., Johnson, M. J., Pomeroy, E. J., Diers, M. D., Lahr, W. S., Draper, G. M., Slipek, N. J., Smeester, B. A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13007-6 · Cited by 232
Treatment of a Mouse Model of ALS by In Vivo Base Editing
Lim, C. K. W., Gapinske, M., Brooks, A. K., Woods, W. S., Powell, J. E., C., M. A. Z., Winter, J., Pérez‐Piñera, P., & Gaj, T. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.01.005 · Cited by 229
Application of CRISPR/Cas9 in Crop Quality Improvement
Liu, Q., Yang, F., Zhang, J., Liu, H., Rahman, S., Islam, S., Ma, W., & She, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22084206 · Cited by 239
Assessing and advancing the safety of CRISPR-Cas tools: from DNA to RNA editing
Tao, J., Bauer, D. E., & Chiarle, R. (2023) · Nature Communications · doi:10.1038/s41467-023-35886-6 · Cited by 232
Transcriptome-wide profiling and quantification of N6-methyladenosine by enzyme-assisted adenosine deamination
Xiao, Y., Liu, S., Ge, R., Wu, Y., He, C., Chen, M., & Tang, W. (2023) · Nature Biotechnology · doi:10.1038/s41587-022-01587-6 · Cited by 199
Recent advances in the CRISPR genome editing tool set
Moon, S. B., Kim, D. Y., Ko, J., & Kim, Y.-S. (2019) · Experimental & Molecular Medicine · doi:10.1038/s12276-019-0339-7 · Cited by 214
Engineering a precise adenine base editor with minimal bystander editing
Chen, L., Zhang, S., Xue, N., Hong, M., Zhang, X., Zhang, D., Yang, J., Bai, S., Huang, Y., Meng, H., et al. (2023) · Nature Chemical Biology · doi:10.1038/s41589-022-01163-8 · Cited by 202
Base editors for simultaneous introduction of C-to-T and A-to-G mutations
Sakata, R. C., Ishiguro, S., Mori, H., Tanaka, M., Tatsuno, K., Ueda, H., Yamamoto, S., Seki, M., Masuyama, N., Nishida, K., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0509-0 · Cited by 197
Prime editing: advances and therapeutic applications
Zhao, Z., Shang, P., Mohanraju, P., & Geijsen, N. (2023) · Trends in biotechnology · doi:10.1016/j.tibtech.2023.03.004 · Cited by 205
Programmable C:G to G:C genome editing with CRISPR-Cas9-directed base excision repair proteins
Chen, L., Park, J. E., Paa, P., Rajakumar, P. D., Prekop, H.-T., Chew, Y. T., Manivannan, S. N., & Chew, W. L. (2021) · Nature Communications · doi:10.1038/s41467-021-21559-9 · Cited by 200
Cytosine base editors with minimized unguided DNA and RNA off-target events and high on-target activity
Yu, Y., Leete, T., Born, D. A., Young, L., Barrera, L. A., Lee, S., Rees, H. A., Ciaramella, G., & Gaudelli, N. M. (2020) · Nature Communications · doi:10.1038/s41467-020-15887-5 · Cited by 195
Gene editing and CRISPR in the clinic: current and future perspectives
Hirakawa, M. P., Krishnakumar, R., Timlin, J. A., Carney, J. P., & Butler, K. S. (2020) · Bioscience Reports · doi:10.1042/bsr20200127 · Cited by 207
Gene-based therapies for neurodegenerative diseases
Sun, J., & Roy, S. (2021) · Nature Neuroscience · doi:10.1038/s41593-020-00778-1 · Cited by 194
Engineered circular ADAR-recruiting RNAs increase the efficiency and fidelity of RNA editing in vitro and in vivo
Yi, Z., Qu, L., Tang, H., Liu, Z., Liu, Y., Tian, F., Wang, C., Zhang, X., Feng, Z., Yu, Y. F., et al. (2022) · Nature Biotechnology · doi:10.1038/s41587-021-01180-3 · Cited by 190
In vivo base editing restores sensory transduction and transiently improves auditory function in a mouse model of recessive deafness
Yeh, W.-H., Shubina-Oleinik, O., Levy, J. M., Pan, B., Newby, G. A., Wornow, M., Burt, R., Chen, J. C., Holt, J. R., & Liu, D. R. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aay9101 · Cited by 183
Development of CRISPR-Cas systems for genome editing and beyond
Zhang, F. (2019) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583519000052 · Cited by 188
Precision genome editing using cytosine and adenine base editors in mammalian cells
Huang, T. P., Newby, G. A., & Liu, D. R. (2021) · Nature Protocols · doi:10.1038/s41596-020-00450-9 · Cited by 175
Precise genomic editing of pathogenic mutations in RBM20 rescues dilated cardiomyopathy
Nishiyama, T., Zhang, Y., Cui, M., Li, H. Z., Sanchez‐Ortiz, E., McAnally, J., Tan, W. H., Kim, J., Chen, K., Xu, L., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.ade1633 · Cited by 174
Perspectives on the Application of Genome-Editing Technologies in Crop Breeding
Hua, K., Zhang, J., Botella, J. R., Ma, C., Kong, F., Liu, B., & Zhu, J. (2019) · Molecular Plant · doi:10.1016/j.molp.2019.06.009 · Cited by 177
Rationally designed APOBEC3B cytosine base editors with improved specificity
Jin, S., Fei, H., Zhu, Z., Luo, Y., Liu, J., Gao, S., Zhang, F., Chen, Y.-H., Wang, Y., & Gao, C. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.07.005 · Cited by 159
A rationally engineered cytosine base editor retains high on-target activity while reducing both DNA and RNA off-target effects
Zuo, E., Sun, Y., Yuan, T., He, B., Zhou, C., Ying, W., Liu, J., Wu, W., Zeng, R., Li, Y., et al. (2020) · Nature Methods · doi:10.1038/s41592-020-0832-x · Cited by 166
Unbiased investigation of specificities of prime editing systems in human cells
Kim, D. Y., Moon, S. B., Ko, J., Kim, Y.-S., & Kim, D. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa764 · Cited by 162
Re-engineering the adenine deaminase TadA-8e for efficient and specific CRISPR-based cytosine base editing
Chen, L., Zhu, B., Ru, G., Meng, H., Yan, Y., Hong, M., Zhang, D., Luan, C., Zhang, S., Wu, H., et al. (2023) · Nature Biotechnology · doi:10.1038/s41587-022-01532-7 · Cited by 156
Current Status and Challenges of DNA Base Editing Tools
Jeong, Y. K., Song, B., & Bae, S. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.07.021 · Cited by 157
Base-edited CAR T cells for combinational therapy against T cell malignancies
Georgiadis, C., Rasaiyaah, J., Gkazi, S. A., Preece, R., Etuk, A., Christi, A., & Qasim, W. (2021) · Leukemia · doi:10.1038/s41375-021-01282-6 · Cited by 140
Increasing the efficiency and targeting range of cytidine base editors through fusion of a single-stranded DNA-binding protein domain
Zhang, X., Chen, L., Zhu, B., Wang, L., Chen, C., Hong, M., Huang, Y., Li, H., Han, H., Cai, B., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0518-8 · Cited by 141
Adenine base editors catalyze cytosine conversions in human cells
Kim, H. S., Jeong, Y. K., Hur, J. K., Kim, J., & Bae, S. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0254-4 · Cited by 127
CRISPR–Cas applications in agriculture and plant research
Tuncel, A., Pan, C., Clem, J. S., Liu, D., & Qi, Y. (2025) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-025-00834-3 · Cited by 145
Advances in CRISPR/Cas-based Gene Therapy in Human Genetic Diseases
Wu, S., Li, Q.-C., Yin, C., Xue, W., & Song, C. (2020) · Theranostics · doi:10.7150/thno.43360 · Cited by 145
Dead Cas Systems: Types, Principles, and Applications
Brezgin, S., Kostyusheva, A., Kostyushev, D. S., & Chulanov, V. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20236041 · Cited by 135
Genome editing for plant research and crop improvement
Zhan, X., Lu, Y., Zhu, J., & Botella, J. R. (2020) · Journal of Integrative Plant Biology · doi:10.1111/jipb.13063 · Cited by 121
Base editing in plants: Current status and challenges
Bharat, S. S., Li, S., Li, J., Yan, L., & Xia, L. (2019) · The Crop Journal · doi:10.1016/j.cj.2019.10.002 · Cited by 126
PE-Designer and PE-Analyzer: web-based design and analysis tools for CRISPR prime editing
Hwang, G., Jeong, Y. K., Habib, O., Hong, S.-A., Lim, K., Kim, J., & Bae, S. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab319 · Cited by 122
CLUSTER guide RNAs enable precise and efficient RNA editing with endogenous ADAR enzymes in vivo
Reautschnig, P., Wahn, N., Wettengel, J., Schulz, A. E., Latifi, N., Vogel, P., Kang, T.-W., Pfeiffer, L. S., Zarges, C., Naumann, U., et al. (2022) · Nature Biotechnology · doi:10.1038/s41587-021-01105-0 · Cited by 118
CRISPR Modeling and Correction of Cardiovascular Disease
Liu, N., & Olson, E. N. (2022) · Circulation Research · doi:10.1161/circresaha.122.320496 · Cited by 120
Brainwide silencing of prion protein by AAV-mediated delivery of an engineered compact epigenetic editor
Neumann, E. N., Bertozzi, T. M., Wu, E., Serack, F. E., Harvey, J. W., Brauer, P. P., Pirtle, C. P., Coffey, A. A., Howard, M., Kamath, N., et al. (2024) · Science · doi:10.1126/science.ado7082 · Cited by 129
Cas12a Base Editors Induce Efficient and Specific Editing with Low DNA Damage Response
Wang, X., Ding, C., Yu, W., Wang, Y., He, S., Yang, B., Xiong, Y., Wei, J., Li, J., Liang, J., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107723 · Cited by 110
Efficient precise in vivo base editing in adult dystrophic mice
Xu, L. M., Zhang, C., Bailin, P. L., Wang, P., Gao, Y., Mohler, P. J., Mokadam, N. A., Ma, J., Arnold, W. D., & Han, R. (2021) · Nature Communications · doi:10.1038/s41467-021-23996-y · Cited by 118
Sharpening the Molecular Scissors: Advances in Gene-Editing Technology
Broeders, M., Herrero-Hernandez, P., Ernst, M. P. T., van der Ploeg, A. T., & Pijnappel, W. W. M. P. (2019) · iScience · doi:10.1016/j.isci.2019.100789 · Cited by 114
Chemical modifications of adenine base editor mRNA and guide RNA expand its application scope
Jiang, T., Henderson, J. M., Coote, K. J., Cheng, Y., Valley, H. C., Zhang, X.-O., Wang, Q., Rhym, L. H., Cao, Y., Newby, G. A., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15892-8 · Cited by 112
Allogeneic CAR-T Therapy Technologies: Has the Promise Been Met?
Lonez, C., & Breman, E. (2024) · Cells · doi:10.3390/cells13020146 · Cited by 119
In vivo cytidine base editing of hepatocytes without detectable off-target mutations in RNA and DNA
Villiger, L., Rothgangl, T., Witzigmann, D., Oka, R., Lin, P. J. C., Qi, W., Janjuha, S., Berk, C., Ringnalda, F., Beattie, M. B., et al. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-020-00671-z · Cited by 105
Tools for experimental and computational analyses of off-target editing by programmable nucleases
Bao, X. R., Pan, Y., Lee, C. M., Davis, T. H., & Bao, G. (2021) · Nature Protocols · doi:10.1038/s41596-020-00431-y · Cited by 106
CRISPR-based therapeutics: current challenges and future applications
Modell, A. E., Lim, D., Nguyen, T. M., Sreekanth, V., & Choudhary, A. (2021) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2021.10.012 · Cited by 114
TCR Redirected T Cells for Cancer Treatment: Achievements, Hurdles, and Goals
Manfredi, F., Cianciotti, B. C., Potenza, A., Tassi, E., Noviello, M., Biondi, A., Ciceri, F., Bonini, C., & Ruggiero, E. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01689 · Cited by 108
Gene therapy for severe combined immunodeficiencies and beyond
Fischer, A., & Hacein‐Bey‐Abina, S. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20190607 · Cited by 108
Eliminating base-editor-induced genome-wide and transcriptome-wide off-target mutations
Wang, L., Xue, W., Zhang, H., Gao, R., Qiu, H.-Y., Wei, J., Zhou, L., Lei, Y.-N., Wu, X., Li, X., et al. (2021) · Nature Cell Biology · doi:10.1038/s41556-021-00671-4 · Cited by 106
Correction of muscular dystrophies by CRISPR gene editing
Chemello, F., Bassel‐Duby, R., & Olson, E. N. (2020) · Journal of Clinical Investigation · doi:10.1172/jci136873 · Cited by 108
Lipid Nanoparticle Spherical Nucleic Acids for Intracellular DNA and RNA Delivery
Sinegra, A. J., Evangelopoulos, M., Park, J., Huang, Z. N., & Mirkin, C. A. (2021) · Nano Letters · doi:10.1021/acs.nanolett.1c01973 · Cited by 100
Safer and efficient base editing and prime editing via ribonucleoproteins delivered through optimized lipid-nanoparticle formulations
Hołubowicz, R., Du, S. W., Felgner, J. H., Šmidák, R., Choi, E. H., Palczewska, G., Menezes, C. R., Dong, Z., Gao, F., Medani, O., et al. (2024) · Nature Biomedical Engineering · doi:10.1038/s41551-024-01296-2 · Cited by 111
Recent advances in chemical modifications of guide RNA, mRNA and donor template for CRISPR-mediated genome editing
Chen, Q., Zhang, Y., & Yin, H. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.10.014 · Cited by 99
Occurrence and Nature of Off-Target Modifications by CRISPR-Cas Genome Editing in Plants
Sturme, M. H. J., van der Berg, J. P., Bouwman, L. M. S., de Schrijver, A., de Maagd, R. A., Kleter, G. A., & Battaglia, E. (2022) · ACS Agricultural Science & Technology · doi:10.1021/acsagscitech.1c00270 · Cited by 99
In vivo HSPC gene therapy with base editors allows for efficient reactivation of fetal γ-globin in β-YAC mice
Li, C., Georgakopoulou, A., Mishra, A., Gil, S., Hawkins, R. D., Yannaki, E., & Lieber, A. (2021) · Blood Advances · doi:10.1182/bloodadvances.2020003702 · Cited by 96
Next-Generation CRISPR Technologies and Their Applications in Gene and Cell Therapy
C., M. A. Z., & Gaj, T. (2020) · Trends in biotechnology · doi:10.1016/j.tibtech.2020.10.010 · Cited by 99
High-purity production and precise editing of DNA base editing ribonucleoproteins
Jang, H.-K., Jo, D. H., Lee, S.-N., Cho, C. S., Jeong, Y. K., Jung, Y., Yu, J., Kim, J. H., Woo, J.-S., & Bae, S. (2021) · Science Advances · doi:10.1126/sciadv.abg2661 · Cited by 93
Off-Target Editing by CRISPR-Guided DNA Base Editors
Park, S., & Beal, P. A. (2019) · Biochemistry · doi:10.1021/acs.biochem.9b00573 · Cited by 95
Engineering TALE-linked deaminases to facilitate precision adenine base editing in mitochondrial DNA
Cho, S.-I., Lim, K., Hong, S., Lee, J., Kim, A., Lim, C. J., Ryou, S., Lee, J. M., Mok, Y. G., Chung, E., et al. (2024) · Cell · doi:10.1016/j.cell.2023.11.035 · Cited by 88
Base and Prime Editing Technologies for Blood Disorders
Antoniou, P., Miccio, A., & Brusson, M. (2021) · Frontiers in Genome Editing · doi:10.3389/fgeed.2021.618406 · Cited by 94
Glycosylase-based base editors for efficient T-to-G and C-to-G editing in mammalian cells
Ye, L., Zhao, D., Li, J., Wang, Y., Li, B., Yang, Y., Hou, X., Wang, H., Wei, Z., Liu, X., et al. (2024) · Nature Biotechnology · doi:10.1038/s41587-023-02050-w · Cited by 91
Rationally Designed Base Editors for Precise Editing of the Sickle Cell Disease Mutation
Chu, S. H., Packer, M. S., Rees, H. A., Lam, D. K., Yu, Y., Marshall, J., Cheng, L.-I., Lam, D., Olins, J., Ran, F. A., et al. (2021) · The CRISPR Journal · doi:10.1089/crispr.2020.0144 · Cited by 79
Comprehensive analysis of prime editing outcomes in human embryonic stem cells
Habib, O., Habib, G., Hwang, G., & Bae, S. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab1295 · Cited by 85
Prediction of off-target specificity and cell-specific fitness of CRISPR-Cas System using attention boosted deep learning and network-based gene feature
Liu, Q., He, D., & Xie, L. (2019) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1007480 · Cited by 86
Click editing enables programmable genome writing using DNA polymerases and HUH endonucleases
da Silva, J. F., Tou, C. J., King, E. M., Eller, M. L., Rufino‐Ramos, D., Ma, L., Cromwell, C. R., Metović, J., Benning, F. M. C., Chao, L. H., et al. (2024) · Nature Biotechnology · doi:10.1038/s41587-024-02324-x · Cited by 86
Enabling large-scale genome editing at repetitive elements by reducing DNA nicking
Smith, C. J., Castanon, O., Said, K., Volf, V., Khoshakhlagh, P., Hornick, A., Ferreira, R., Wu, C., Güell, M., Garg, S., et al. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa239 · Cited by 83
Deep latency: A new insight into a functional HIV cure
Elsheikh, M. M., Tang, Y., Li, D., & Jiang, G. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.06.020 · Cited by 84
Single C-to-T substitution using engineered APOBEC3G-nCas9 base editors with minimum genome- and transcriptome-wide off-target effects
Lee, S., Ding, N., Sun, Y., Yuan, T., Li, J., Yuan, Q., Liu, L., Yang, J., Wang, Q., Kolomeisky, A. B., et al. (2020) · Science Advances · doi:10.1126/sciadv.aba1773 · Cited by 81
Multiplex base- and prime-editing with drive-and-process CRISPR arrays
Yuan, Q., & Gao, X. (2022) · Nature Communications · doi:10.1038/s41467-022-30514-1 · Cited by 85
Virus-Like Particle Mediated CRISPR/Cas9 Delivery for Efficient and Safe Genome Editing
Lyu, P., Wang, L., & Lu, B. (2020) · Life · doi:10.3390/life10120366 · Cited by 79

Authors: Grünewald, J., Zhou, R., Garcia, S. P., Iyer, S., Lareau, C. A., Aryee, M. J., & Joung, J. K.
Affiliations: Harvard University (US)
Massachusetts General Hospital (US)
Corresponding author: Joung, J. Keith
ORCID: Grünewald, Julian
Zhou, Ronghao
Garcia, Sara P.
Iyer, Sowmya
Lareau, Caleb A.
Aryee, Martin J.
Joung, J. Keith
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2019-04-17
Volume: 569
Issue: 7756
Pages: 433-437
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/s41586-019-1161-z
PMC: PMC6657343
OpenAlex: W2939749480
Cited by: 663
References: 37
Citations by year: 2026: 66 · 2025: 74 · 2024: 80 · 2023: 100 · 2022: 84 · 2021: 106 · 2020: 104 · 2019: 48
FWCI: 28.72
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Digital Access to Scholarship at Harvard (DASH) (Harvard University) (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: National Human Genome Research Institute (RM1HG009490)
National Institute of General Medical Sciences (R35GM118158)
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 › RNA Interference and Gene Delivery
Keywords: cytosine base editors, APOBEC1, RNA editing, off-target effects, adenine base editors, deaminase activity, human cells
MeSH terms: APOBEC-1 Deaminase, Gene Editing, Animals, Base Sequence, Cytosine, Deamination, Humans, Mutation, RNA, Substrate Specificity, RNA Editing, Rats, Hep G2 Cells, HEK293 Cells, Transcriptome, CRISPR-Cas Systems

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

Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks