The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases
Open accessAbstract
CRISPR RNA-guided nucleases (RGNs) are widely used genome-editing reagents, but methods to delineate their genome-wide, off-target cleavage activities have been lacking. Here we describe an approach for global detection of DNA double-stranded breaks (DSBs) introduced by RGNs and potentially other nucleases. This method, called genome-wide, unbiased identification of DSBs enabled by sequencing (GUIDE-seq), relies on capture of double-stranded oligodeoxynucleotides into DSBs. Application of GUIDE-seq to 13 RGNs in two human cell lines revealed wide variability in RGN off-target activities and unappreciated characteristics of off-target sequences. The majority of identified sites were not detected by existing computational methods or chromatin immunoprecipitation sequencing (ChIP-seq). GUIDE-seq also identified RGN-independent genomic breakpoint 'hotspots'. Finally, GUIDE-seq revealed that truncated guide RNAs exhibit substantially reduced RGN-induced, off-target DSBs. Our experiments define the most rigorous framework for genome-wide identification of RGN off-target effects to date and provide a method for evaluating the safety of these nucleases before clinical use.
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 cited source doesn’t support the claim as written.
In the citing paper
“A primary limitation of GUIDE-seq is relevant to the low delivery efficiency of dsODNs into cells, which results in detection of only 30%–50% of all the DSBs (Tsai et al., 2015; Pan et al., 2022).”
From Off-target effects in CRISPR/Cas9 gene editing (2023) · cites this paper as Tsai et al., 2015
Checked by a reasoning model — may be wrong.
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
“Off-target profiling of AsCas12a-crRNA+11 genome editing in HEK293/3272-26A>G cells18,42 showed very high specificity, as demonstrated by exclusive editing of the 3272-26A>G CFTR locus, while non-specific cleavages in the second allele, or any other genomic loci, could not be detected (Fig. 2c and Supplementary Fig. 4c).”
From Allele specific repair of splicing mutations in cystic fibrosis through AsCas12a genome editing (2019) · cites this paper as [42]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“While cleavage at sites with perfect complementarity to the protospacer domain of the gRNA typically occurs with highest efficiency, cleavage at sites having one to several bases of mismatch with the gRNA can occur. These undesired cleavage events are called “off-target effects” (OTEs)10, and their existence should be minimized for therapeutic applications of genome editing technologies.”
From A high-fidelity Cas9 mutant delivered as a ribonucleoprotein complex enables efficient gene editing in human hematopoietic stem and progenitor cells (2018) · cites this paper as [10]
The cited source says what the claim attributes to it.
In the citing paper
“The GUIDE-seq procedure10 can be used to empirically identify real off-target sites in cells.”
From A high-fidelity Cas9 mutant delivered as a ribonucleoprotein complex enables efficient gene editing in human hematopoietic stem and progenitor cells (2018) · cites this paper as [10]
The cited source says what the claim attributes to it.
In the citing paper
“GUIDE-seq can detect off-target sites with indel frequencies as low as 0.03% (Tsai et al., 2015).”
From Off-target effects in CRISPR/Cas9 gene editing (2023) · cites this paper as Tsai et al., 2015
The cited source says what the claim attributes to it.
In the citing paper
“GUIDE-seq is more sensitive than the IDLV method because dsODNs integrate more efficiently and precisely into DSBs, while the integration events of IDLV is low in number and can distribute as far as 500bp away from the actual DSB sites (Tsai et al., 2015; Cromer et al., 2023).”
From Off-target effects in CRISPR/Cas9 gene editing (2023) · cites this paper as Tsai et al., 2015
The cited source says what the claim attributes to it.
In the citing paper
“However, other publications observed a much lower validation rate (Cencic et al., 2014; Duan et al., 2014; Tsai et al., 2015).”
From Off-target effects in CRISPR/Cas9 gene editing (2023) · cites this paper as Tsai et al., 2015
The cited source says what the claim attributes to it.
In the citing paper
“These studies indicated that Cas9 could associate with genomic loci without exerting its nuclease function, deposing a major caveat in Cas9 ChIP-Seq-based off-target detection assay.”
From Off-target effects in CRISPR/Cas9 gene editing (2023) · cites this paper as Tsai et al., 2015
The cited source says what the claim attributes to it.
In the citing paper
“Interestingly, compared to cell-based methods such as GUIDE-seq (see next section) (Tsai et al., 2015), Extru-seq exhibited much lower false negative rate (2.3% versus 29%) (Kwon et al., 2023).”
From Off-target effects in CRISPR/Cas9 gene editing (2023) · cites this paper as Tsai et al., 2015
In the citing paper
“Using the standard Guide-seq protocol, we detected only the Fah target site and one off-target site (defined as Guide-seq off-target site 1, or GOT1) (Supplementary Data Set 1).”
From Adenine base editing in an adult mouse model of tyrosinaemia (2019) · cites this paper as [23]
In the citing paper
“However, silicon methods can only identify part of the off-target cleavage.48”
From CRISPR-Cas9: a new and promising player in gene therapy (2015) · cites this paper as [48]
In the citing paper
“The major barrier of clinical use of CRISPR/Cas9 is its off-target effects [81,82,83].”
From Viral Delivery Systems for CRISPR (2019) · cites this paper as [81]
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
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607
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
Fast and accurate long-read alignment with Burrows-Wheeler transform.
Li, H., & Durbin, R. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp698 · Cited by 12,063
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
Development and Applications of CRISPR-Cas9 for Genome Engineering
Hsu, P. D., Lander, E. S., & Zhang, F. (2014) · Cell · doi:10.1016/j.cell.2014.05.010 · Cited by 5,762
DNA targeting specificity of RNA-guided Cas9 nucleases
Hsu, P. D., Scott, D. A., Weinstein, J. A., Ran, F. A., Konermann, S., Agarwala, V., Li, Y., Fine, E. J., Wu, X., Shalem, O., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2647 · Cited by 4,741
Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity
Ran, F. A., Hsu, P. D., Lin, C.-Y., Gootenberg, J. S., Konermann, S., Trevino, A. E., Scott, D. A., Inoue, A., Matoba, S., Zhang, Y., et al. (2013) · Cell · doi:10.1016/j.cell.2013.08.021 · Cited by 3,299
High-Frequency off-Target Mutagenesis Induced by CRISPR-Cas Nucleases in Human Cells
Fu, Y., Foden, J. A., Khayter, C., Maeder, M. L., Reyon, D., Joung, J. K., & Sander, J. D. (2013) · Nature Biotechnology · doi:10.1038/nbt.2623 · Cited by 3,292
Self-citationCRISPR-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
Self-citationRNA-guided editing of bacterial genomes using CRISPR-Cas systems
Jiang, W., Bikard, D., Cox, D., Zhang, F., & Marraffini, L. A. (2013) · Nature Biotechnology · doi:10.1038/nbt.2508 · Cited by 2,429
Flagged first, then by citations
Cited by
Sorted by citations
Items 601–700 of 1,009
Ma, L., Ruan, J., Song, J. W., Wen, L., Yang, D., Zhao, J., Xia, X., Chen, Y. E., Zhang, J., & Xu, J. (2020) · Nature Communications · doi:10.1038/s41467-020-19842-2 · Cited by 60
Schmidt, M. J., Gupta, A. K., Bednarski, C., Gehrig-Giannini, S., Richter, F. M., Pitzler, C., Gamalinda, M., Galonska, C., Takeuchi, R., Wang, K., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24454-5 · Cited by 58
ON-Target Adverse Events of CRISPR-Cas9 Nuclease: More Chaotic than Expected
Boutin, J., Cappellen, D., Rosier, J., Amintas, S., Dabernat, S., Bedel, A., & Moreau‐Gaudry, F. (2022) · The CRISPR Journal · doi:10.1089/crispr.2021.0120 · Cited by 59
CRISPR-DIPOFF: an interpretable deep learning approach for CRISPR Cas-9 off-target prediction
Toufikuzzaman, M., Samee, M. A. H., & Rahman, M. S. (2024) · Briefings in Bioinformatics · doi:10.1093/bib/bbad530 · Cited by 60
Abbasi, A. F., Asim, M. N., & Dengel, A. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-024-06013-w · Cited by 60
Breton, C. A., Clark, P., Wang, L., Greig, J. A., & Wilson, J. M. (2020) · BMC Genomics · doi:10.1186/s12864-020-6655-4 · Cited by 60
Ou, L., Przybilla, M. J., Ahlat, O., Kim, S., Overn, P., Jarnes, J., O’Sullivan, M. G., & Whitley, C. B. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.03.018 · Cited by 56
Precision medicine: drowning in a regulatory soup?
Nicol, D., Bubela, T. M., Chalmers, D., Charbonneau, J., Critchley, C. R., Dickinson, J. L., Fleming, J., Hewitt, A. W., Kaye, J. S., Liddicoat, J., et al. (2016) · Journal of Law and the Biosciences · doi:10.1093/jlb/lsw018 · Cited by 59
Application of the gene editing tool, CRISPR-Cas9, for treating neurodegenerative diseases
Kolli, N., Lü, M., Maiti, P., Rossignol, J., & Dunbar, G. L. (2017) · Neurochemistry International · doi:10.1016/j.neuint.2017.07.007 · Cited by 59
CRISPR/Cas mediated epigenome editing for cancer therapy
Ansari, I., Chaturvedi, A., Chitkara, D., & Singh, S. P. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.12.018 · Cited by 58
Charlier, J., Nadon, R., & Makarenkov, V. (2021) · Bioinformatics · doi:10.1093/bioinformatics/btab112 · Cited by 59
Harnessing DSB repair to promote efficient homology-dependent and -independent prime editing
Peterka, M., Akrap, N., Li, S., Wimberger, S., Hsieh, P.-P., Degtev, D., Bestas, B., Barr, J., van de Plassche, S., Mendoza-García, P., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28771-1 · Cited by 57
Low, B. E., Hosur, V., Lesbirel, S., & Wiles, M. V. (2022) · Scientific Reports · doi:10.1038/s41598-022-09445-w · Cited by 57
Medium-chain alkane biodegradation and its link to some unifying attributes of alkB genes diversity
Fenibo, E. O., Selvarajan, R., Abia, A. L. K., & Matambo, T. S. (2023) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2023.162951 · Cited by 56
The Conspicuity of CRISPR-Cpf1 System as a Significant Breakthrough in Genome Editing
Bayat, H., Modarressi, M. H., & Rahimpour, A. (2017) · Current Microbiology · doi:10.1007/s00284-017-1406-8 · Cited by 56
CRISPR-Based Tools in Immunity
Simeonov, D. R., & Marson, A. (2019) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042718-041522 · Cited by 57
Highly efficient single base editing in Aspergillus niger with CRISPR/Cas9 cytidine deaminase fusion
Huang, L., Dong, H., Zheng, J., Wang, B., & Pan, L. (2019) · Microbiological Research · doi:10.1016/j.micres.2019.03.007 · Cited by 59
Rose, J. C., Popp, N. A., Richardson, C. D., Stephany, J. J., Mathieu, J., Wei, C. T., Corn, J. E., Maly, D. J., & Fowler, D. M. (2020) · Nature Communications · doi:10.1038/s41467-020-16542-9 · Cited by 61
Next-generation cell therapies: the emerging role of CAR-NK cells
Başar, R., Daher, M., & Rezvani, K. (2020) · Hematology · doi:10.1182/hematology.2020002547 · Cited by 57
Evaluation of CRISPR gene-editing tools in zebrafish
Uribe‐Salazar, J. M., Kaya, G., Sekar, A., Weyenberg, K., Ingamells, C., & Dennis, M. Y. (2022) · BMC Genomics · doi:10.1186/s12864-021-08238-1 · Cited by 57
Systematic decomposition of sequence determinants governing CRISPR/Cas9 specificity
Fu, R., He, W., Dou, J., Villarreal, O. D., Bedford, E., Wang, H. H., Hou, C., Zhang, L., Wang, Y., Ma, D., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28028-x · Cited by 59
Improving the sensitivity of in vivo CRISPR off-target detection with DISCOVER-Seq+
Zou, R. S., Liu, Y., Gaido, O. E. R., Konig, M. F., Mog, B. J., Shen, L. L., Avilés-Vázquez, F. J., Marín-González, A., & Ha, T. (2023) · Nature Methods · doi:10.1038/s41592-023-01840-z · Cited by 57
Amen, R. A., Hassan, Y. M., Essmat, R. A., Ahmed, R. H., Azab, M. M., Shehata, N. R., Elgazzar, M. M., & El-Sayed, W. M. (2025) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-025-10573-8 · Cited by 56
Nakagawa, Y., Sakuma, T., Sakamoto, T., Ohmuraya, M., Nakagata, N., & Yamamoto, T. (2015) · BMC Biotechnology · doi:10.1186/s12896-015-0144-x · Cited by 55
Heritability of targeted gene modifications induced by plant-optimized CRISPR systems
Mao, Y., Botella, J. R., & Zhu, J. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2380-1 · Cited by 55
The Hope and Hype of CRISPR-Cas9 Genome Editing
Musunuru, K. (2017) · JAMA Cardiology · doi:10.1001/jamacardio.2017.1713 · Cited by 59
Garczynski, S. F., Martin, J. A., Griset, M., Willett, L. S., Cooper, W. R., Swisher, K. D., & Unruh, T. R. (2017) · Journal of Economic Entomology · doi:10.1093/jee/tox166 · Cited by 55
Protein Inhibitors of CRISPR-Cas9
Bondy‐Denomy, J. (2017) · ACS Chemical Biology · doi:10.1021/acschembio.7b00831 · Cited by 56
CRISPR technologies for the treatment of Duchenne muscular dystrophy
Choi, E., & Koo, T. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.04.002 · Cited by 57
Cytosine base editing systems with minimized off-target effect and molecular size
Li, A., Mitsunobu, H., Yoshioka, S., Suzuki, T., Kondo, A., & Nishida, K. (2022) · Nature Communications · doi:10.1038/s41467-022-32157-8 · Cited by 57
Genome-wide detection of CRISPR editing in vivo using GUIDE-tag
Liang, S.-Q., Liu, P., Smith, J. L., Mintzer, E., Maitland, S., Dong, X., Yang, Q., Lee, J., Haynes, C. M., Zhu, L. J., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28135-9 · Cited by 54
Find and cut-and-transfer (FiCAT) mammalian genome engineering
Pallarès-Masmitjà, M., Ivančić, D., Mir-Pedrol, J., Jaraba-Wallace, J., Tagliani, T., Oliva, B., Rahmeh, A. A., Sánchez-Mejías, A., & Güell, M. (2021) · Nature Communications · doi:10.1038/s41467-021-27183-x · Cited by 57
Decorating chromatin for enhanced genome editing using CRISPR-Cas9
Chen, E., Lin-Shiao, E., Trinidad, M. I., Doost, M. S., Colognori, D., & Doudna, J. A. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2204259119 · Cited by 57
Efficient plant genome engineering using a probiotic sourced CRISPR-Cas9 system
Zhong, Z., Liu, G., Tang, Z., Xiang, S., Yang, L., Huang, L., He, Y., Fan, T., Liu, S., Zheng, X., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41802-9 · Cited by 58
Synthesis of an arrayed sgRNA library targeting the human genome
Schmidt, T., Schmid-Burgk, J. L., & Hornung, V. (2015) · Scientific Reports · doi:10.1038/srep14987 · Cited by 54
Gene Editing of Human Hematopoietic Stem and Progenitor Cells: Promise and Potential Hurdles
Yu, K., Natanson, H., & Dunbar, C. E. (2016) · Human Gene Therapy · doi:10.1089/hum.2016.107 · Cited by 59
Yang, H., & Chen, P. (2017) · Virus Research · doi:10.1016/j.virusres.2017.06.010 · Cited by 54
CRISPR/Cas9 cleavage efficiency regression through boosting algorithms and Markov sequence profiling
Peng, H., Zheng, Y., Blumenstein, M., Tao, D., & Li, J. (2018) · Bioinformatics · doi:10.1093/bioinformatics/bty298 · Cited by 57
Peng, H., Zheng, Y., Zhao, Z., Liu, T., & Li, J. (2018) · Bioinformatics · doi:10.1093/bioinformatics/bty558 · Cited by 57
Computational Tools and Resources Supporting CRISPR-Cas Experiments
Śledziński, P., Nowaczyk, M., & Olejniczak, M. (2020) · Cells · doi:10.3390/cells9051288 · Cited by 57
A systematic genome-wide mapping of oncogenic mutation selection during CRISPR-Cas9 genome editing
Sinha, S., Barbosa, K., Cheng, K., Leiserson, M. D. M., Jain, P., Deshpande, A. J., Wilson, D. M., Ryan, B. M., Luo, J., Ronai, Z. A., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26788-6 · Cited by 56
The comparison of ZFNs, TALENs, and SpCas9 by GUIDE-seq in HPV-targeted gene therapy
Cui, Z., Liu, H., Zhang, H., Huang, Z., Tian, R., Li, L., Fan, W., Chen, Y., Chen, L., Zhang, S., et al. (2021) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2021.08.008 · Cited by 53
Massively parallel knock-in engineering of human T cells
Dai, X., Park, J. J.-Y., Du, Y., Na, Z., Lam, S. Z., Chow, R. D.-W., Renauer, P. A., Gu, J., Shan, X., Chu, Z., et al. (2023) · Nature Biotechnology · doi:10.1038/s41587-022-01639-x · Cited by 56
Flores, C., Mojadidi, M., Phillips, J., Kuo, C. Y., Lai, S. Y., Lill, G. R., Cooper, A. R., Kaufman, M. L., Urbinati, F., Wang, X., et al. (2016) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2016.52 · Cited by 53
Bouwman, B. A. M., & Crosetto, N. (2018) · Genes · doi:10.3390/genes9120632 · Cited by 65
CRISPR mediated genome engineering to develop climate smart rice: Challenges and opportunities
Biswal, A. K., Mangrauthia, S. K., Reddy, M. R., & Yugandhar, P. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.04.005 · Cited by 56
Detection and Modulation of DNA Translocations During Multi-Gene Genome Editing in T Cells
Bothmer, A., Gareau, K. W., Abdulkerim, H. S., Buquicchio, F. A., Cohen, L. A., Viswanathan, R., Zuris, J. A., Marco, E., Fernández, C. A., Myer, V. E., et al. (2020) · The CRISPR Journal · doi:10.1089/crispr.2019.0074 · Cited by 56
High-level correction of the sickle mutation is amplified in vivo during erythroid differentiation
Magis, W., DeWitt, M. A., Wyman, S. K., Vu, J. T., Heo, S., Shao, S. J., Hennig, F., Romero, Z. G., Campo-Fernández, B., Said, S., et al. (2022) · iScience · doi:10.1016/j.isci.2022.104374 · Cited by 53
Bollen, Y., Post, J. B., Koo, B., & Snippert, H. J. G. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky571 · Cited by 53
Genetic Renal Diseases: The Emerging Role of Zebrafish Models
Elmonem, M. A., Berlingerio, S. P., van den Heuvel, L. P., de Witte, P. A. M., Lowe, M., & Levtchenko, E. N. (2018) · Cells · doi:10.3390/cells7090130 · Cited by 59
AmpUMI: design and analysis of unique molecular identifiers for deep amplicon sequencing
Clement, K., Farouni, R., Bauer, D. E., & Pinello, L. (2018) · Bioinformatics · doi:10.1093/bioinformatics/bty264 · Cited by 52
CRISPR/Cas system: An emerging technology in stem cell research
Valenti, M. T., Serena, M., Carbonare, L. D., & Zipeto, D. (2019) · World Journal of Stem Cells · doi:10.4252/wjsc.v11.i11.937 · Cited by 54
Historic Overview of Genetic Engineering Technologies for Human Gene Therapy
Tamura, R., & Toda, M. (2020) · Neurologia medico-chirurgica · doi:10.2176/nmc.ra.2020-0049 · Cited by 52
Anticipating and Identifying Collateral Damage in Genome Editing
Burgio, G., & Teboul, L. (2020) · Trends in Genetics · doi:10.1016/j.tig.2020.09.011 · Cited by 53
Vavassori, V., Mercuri, E., Marcovecchio, G. E., Castiello, M. C., Schiroli, G., Albano, L., Margulies, C. M., Buquicchio, F. A., Fontana, E., Beretta, S., et al. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202013545 · Cited by 52
A highly specific CRISPR-Cas12j nuclease enables allele-specific genome editing
Wang, Y., Qi, T., Liu, J., Yang, Y., Wang, Z., Wang, Y., Wang, T., Li, M., Li, M., Lu, D., et al. (2023) · Science Advances · doi:10.1126/sciadv.abo6405 · Cited by 56
Sufyan, M., Daraz, U., Hyder, S., Zulfiqar, U., Iqbal, R., Eldin, S. M., Rafiq, F., Mahmood, N., Shahzad, K., Uzair, M., et al. (2023) · Functional & Integrative Genomics · doi:10.1007/s10142-023-01036-w · Cited by 55
Yin, J., Frick, L. D., Scheidmann, M. C., Liu, T., Trevisan, C., Dhingra, A., Spinelli, A., Wu, Y., Yao, L., Vena, D. L., et al. (2024) · Nature Biomedical Engineering · doi:10.1038/s41551-024-01278-4 · Cited by 55
Wong, N., John, S., Nussenzweig, A., & Canela, A. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0644-5_2 · Cited by 51
Chen, Y., Luo, S., Hu, Y., Mao, B., Wang, X., Lu, Z., Shan, Q., Zhang, J., Wang, S., Feng, G., et al. (2024) · Cell · doi:10.1016/j.cell.2024.06.020 · Cited by 50
CRISPR: a versatile tool for both forward and reverse genetics research
Gurumurthy, C. B., Grati, M., Ohtsuka, M., Schilit, S. L. P., Quadros, R. M., & Liu, X. Z. (2016) · Human Genetics · doi:10.1007/s00439-016-1704-4 · Cited by 52
Cutting Edge Genetics: CRISPR/Cas9 Editing of Plant Genomes
Soyars, C. L., Peterson, B. A., Burr, C. A., & Nimchuk, Z. L. (2018) · Plant and Cell Physiology · doi:10.1093/pcp/pcy079 · Cited by 50
Enhanced Genome Editing with Cas9 Ribonucleoprotein in Diverse Cells and Organisms
Farboud, B., Jarvis, E., Roth, T. L., Shin, J. J., Corn, J. E., Marson, A., Meyer, B. J., Patel, N. H., & Hochstrasser, M. L. (2018) · Journal of Visualized Experiments · doi:10.3791/57350 · Cited by 52
Clinical applications of CRISPR‐based genome editing and diagnostics
Foss, D. V., Hochstrasser, M. L., & Wilson, R. C. (2019) · Transfusion · doi:10.1111/trf.15126 · Cited by 51
Targeted genomic CRISPR-Cas9 screen identifies MAP4K4 as essential for glioblastoma invasion
Prolo, L. M., Li, A., Owen, S. F., Parker, J. J., Foshay, K. M., Nitta, R. T., Morgens, D. W., Bolin, S., Wilson, C., Leonel, J. C. M. V., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-50160-w · Cited by 50
Tran, N. T., Danner, E., Li, X., Graf, R., Lebedin, M., de la Rosa, K., Kühn, R., Rajewsky, K., & Chu, V. T. (2022) · Science Advances · doi:10.1126/sciadv.abm9106 · Cited by 49
Connolly, J. B., Mumford, J. D., Fuchs, S., Turner, G., Beech, C., North, A. R., & Burt, A. (2021) · Malaria Journal · doi:10.1186/s12936-021-03674-6 · Cited by 50
Genome editing in the mouse brain with minimally immunogenic Cas9 RNPs
Stahl, E. C., Sabo, J. K., Kang, M. H., Allen, R., Applegate, E., Kim, S., Kwon, Y., Seth, A., Lemus, N., Salinas-Rios, V., et al. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.06.019 · Cited by 51
Golikova, E., Alshevskaya, A., Alrhmoun, S., Sivitskaya, N. A., & Sennikov, S. V. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05703-9 · Cited by 50
Gutiérrez-Guerrero, A., Sánchez-Hernández, S., Galvani, G., Pinedo-Gomez, J., Martín-Guerra, R., Sánchez‐Gilabert, A., Aguilar-González, A., Cobo, M., Gregory, P. D., Holmes, M. C., et al. (2017) · Human Gene Therapy · doi:10.1089/hum.2017.047 · Cited by 50
A Genome-Wide CRISPR Library for High-Throughput Genetic Screening in Drosophila Cells
Bassett, A. R., Kong, L., & Liu, J. (2015) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2015.03.011 · Cited by 48
Unleashing the Therapeutic Potential of CAR-T Cell Therapy Using Gene-Editing Technologies.
Jung, I.-Y., & Lee, J. (2018) · Europe PMC (PubMed Central) · doi:10.14348/molcells.2018.0242 · Cited by 49
Inhibition of CRISPR-Cas12a DNA targeting by nucleosomes and chromatin
Strohkendl, I., Saifuddin, F. A., Gibson, B. A., Rosen, M. K., Russell, R., & Finkelstein, I. J. (2021) · Science Advances · doi:10.1126/sciadv.abd6030 · Cited by 48
Synergistic engineering of CRISPR-Cas nucleases enables robust mammalian genome editing
Chen, Y., Hu, Y., Wang, X., Luo, S., Yang, N., Chen, Y., Li, Z., Zhou, Q., & Li, W. (2022) · The Innovation · doi:10.1016/j.xinn.2022.100264 · Cited by 49
Zou, R. S., Marín-González, A., Liu, Y., Liu, H. B., Shen, L. L., Dveirin, R. K., Luo, J. X. J., Kalhor, R., & Ha, T. (2022) · Nature Cell Biology · doi:10.1038/s41556-022-00975-z · Cited by 48
Bidirectional epigenetic editing reveals hierarchies in gene regulation
Pacalin, N. M., Steinhart, Z., Shi, Q., Belk, J. A., Dorovskyi, D., Kraft, K., Parker, K. R., Shy, B. R., Marson, A., & Chang, H. Y. (2024) · Nature Biotechnology · doi:10.1038/s41587-024-02213-3 · Cited by 49
Genome engineering in ophthalmology: Application of CRISPR/Cas to the treatment of eye disease
Hung, S. S. C., McCaughey, T., Swann, O. G., Pébay, A., & Hewitt, A. W. (2016) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2016.05.001 · Cited by 49
Targeted Genome Replacement via Homology-directed Repair in Non-dividing Cardiomyocytes
Ishizu, T., Higo, S., Masumura, Y., Kohama, Y., Shiba, M., Higo, T., Shibamoto, M., Nakagawa, A., Morimoto, S., Takashima, S., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-09716-x · Cited by 50
CRISPR therapeutic tools for complex genetic disorders and cancer (Review)
Baliou, S., Adamaki, M., Kyriakopoulos, A. M., Spandidos, D. A., Panayiotidis, M. I., Christodoulou, I., & Zoumpourlis, V. C. (2018) · International Journal of Oncology · doi:10.3892/ijo.2018.4434 · Cited by 55
Nakajima, K., Zhou, Y., Tomita, A., Hirade, Y., Gurumurthy, C. B., & Nakada, S. (2017) · Genome Research · doi:10.1101/gr.226027.117 · Cited by 48
Concerns regarding ‘off-target’activity of genome editing endonucleases
Kadam, U. S., Shelake, R. M., Chavhan, R. L., & Suprasanna, P. (2018) · Plant Physiology and Biochemistry · doi:10.1016/j.plaphy.2018.03.027 · Cited by 47
Benchmarking deep learning methods for predicting CRISPR/Cas9 sgRNA on- and off-target activities
Zhang, G., Luo, Y., Dai, X., & Dai, Z. (2023) · Briefings in Bioinformatics · doi:10.1093/bib/bbad333 · Cited by 47
Gene Editing of Hematopoietic Stem Cells: Hopes and Hurdles Toward Clinical Translation
Ferrari, S., Vavassori, V., Canarutto, D., Jacob, A., Castiello, M. C., Omer, A., & Genovese, P. (2021) · Frontiers in Genome Editing · doi:10.3389/fgeed.2021.618378 · Cited by 52
In vivo correction of cystic fibrosis mediated by PNA nanoparticles
Piotrowski-Daspit, A. S., Barone, C., Lin, C.-Y., Deng, Y., Wu, D. H., Binns, T. C., Xu, E., Ricciardi, A. S., Putman, R., Garrison, A., et al. (2022) · Science Advances · doi:10.1126/sciadv.abo0522 · Cited by 49
Tao, Y., Lamas, V., Du, W., Zhu, W., Li, Y., Whittaker, M. N., Zuris, J. A., Thompson, D. B., Rameshbabu, A. P., Shu, Y., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-40476-7 · Cited by 47
Luft, C., & Ketteler, R. (2015) · SLAS DISCOVERY · doi:10.1177/1087057115579638 · Cited by 47
CRISPR/Cas9 System: A Bacterial Tailor for Genomic Engineering
Lone, B. A., Karna, S. K. L., Ahmad, F., Shahi, N., & Pokharel, Y. R. (2018) · Genetics Research International · doi:10.1155/2018/3797214 · Cited by 48
Chen, Y., Jiang, H., Wang, T., He, D., Tian, R., Cui, Z., Tian, X., Gao, Q., Ma, X., Yang, J., et al. (2020) · Antiviral Research · doi:10.1016/j.antiviral.2020.104794 · Cited by 47
CRISPR-Editing Therapy for Duchenne Muscular Dystrophy
Chemello, F., Olson, E. N., & Bassel‐Duby, R. (2023) · Human Gene Therapy · doi:10.1089/hum.2023.053 · Cited by 47
Application progress of CRISPR/Cas9 genome-editing technology in edible fungi
Zhang, Y., Chen, S., Yang, L., & Zhang, Q. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1169884 · Cited by 48
Raikwar, S. P., Kikkeri, N. S., Sakuru, R. C., Saeed, D., Zahoor, H., Premkumar, K., Mentor, S., Thangavel, R., Dubova, I., Ahmed, M. E., et al. (2019) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-019-09849-y · Cited by 48
A Three-Way Combinatorial CRISPR Screen for Analyzing Interactions among Druggable Targets
Zhou, P., Chan, B. K. C., Wan, Y. K., Yuen, C. T. L., Choi, G. C. G., Li, X., Tong, C. S. W., Zhong, S. S. W., Sun, J., Bao, Y., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108020 · Cited by 46
Self-citationJiang, L., Ingelshed, K., Shen, Y., Boddul, S. V., Iyer, V. S., Kasza, Z., Sedimbi, S. K., Lane, D. P., & Wermeling, F. (2021) · Cancer Research · doi:10.1158/0008-5472.can-21-1692 · Cited by 47
Engineered Cas12a-Plus nuclease enables gene editing with enhanced activity and specificity
Huang, H., Huang, G., Tan, Z., Hu, Y., Shan, L., Zhou, J., Zhang, X., Ma, S., Lv, W., Huang, T., et al. (2022) · BMC Biology · doi:10.1186/s12915-022-01296-1 · Cited by 46
CRISPR-Cas9 in vivo gene editing for transthyretin amyloidosis
Gillmore, J. D., Gane, E. J., Täubel, J., Kao, J., Fontana, M., Maitland, M. L., Seitzer, J. L., O'Connell, D., Walsh, K. R., Wood, K. M., et al. (2022) · Yearbook of pediatric endocrinology · doi:10.1530/ey.19.14.13 · Cited by 46
Kulcsár, P. I., Tálas, A., Tóth, E., Nyeste, A., Ligeti, Z., Welker, Z., & Welker, E. (2020) · Nature Communications · doi:10.1038/s41467-020-15021-5 · Cited by 45
Efficient precise integration of large DNA sequences with 3′-overhang dsDNA donors using CRISPR/Cas9
Han, W., Li, Z., Guo, Y., He, K., Li, W., Xu, C., Ge, L., He, M., Yin, X., Zhou, J., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2221127120 · Cited by 45
An adenine base editor variant expands context compatibility
Xiao, Y., Wu, Y., & Tang, W. (2024) · Nature Biotechnology · doi:10.1038/s41587-023-01994-3 · Cited by 48
Single-molecule imaging and tracking of molecular dynamics in living cells
Li, N., Zhao, R., Sun, Y., Ye, Z., He, K., & Fang, X. (2017) · National Science Review · doi:10.1093/nsr/nww055 · Cited by 47
Initiation of homologous recombination at DNA nicks
Maizels, N., & Davis, L. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky588 · Cited by 50
Metadata
- Authors
- 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., Aryee, M. J., & Joung, J. K.
- Affiliations
- Harvard University (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Tsai, Shengdar Q
- Joung, J Keith
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2014-12-16
- Volume
- 33
- Issue
- 2
- Pages
- 187-197
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC4320685
- OpenAlex
- W2003797386
- Cited by
- 2,268
- References
- 39
- Citations by year
- 2026: 189 · 2025: 211 · 2024: 196 · 2023: 191 · 2022: 208 · 2021: 211 · 2020: 231 · 2019: 186 · 2018: 187 · 2017: 177 · 2016: 172 · 2015: 105 · 2014: 1
- FWCI
- 62.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institute of General Medical Sciences (DP1GM105378, R01GM088040, F32GM105189)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR063070)
- National Center for Chronic Disease Prevention and Health Promotion (DP1 GM105378)
- 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
- GUIDE-seq, CRISPR-Cas nucleases, off-target cleavage, DNA double-strand breaks, genome-wide characterization, genome editing safety
- MeSH terms
- RNA, Guide, CRISPR-Cas Systems, Cell Line, Humans, Oligodeoxyribonucleotides, Genome, Human, RNA Editing, DNA Breaks, Double-Stranded, High-Throughput Nucleotide Sequencing, 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
