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 701–800 of 1,009
Bridge Helix of Cas9 Modulates Target DNA Cleavage and Mismatch Tolerance
Babu, K., Amrani, N., Jiang, W., Yogesha, S. D., Nguyen, R., Qin, P. Z., & Rajan, R. (2019) · Biochemistry · doi:10.1021/acs.biochem.8b01241 · Cited by 47
Variability in Genome Editing Outcomes: Challenges for Research Reproducibility and Clinical Safety
Teboul, L., Hérault, Y., Wells, S. E., Qasim, W., & Pavlovic, G. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.03.015 · Cited by 47
Cas12a variants designed for lower genome-wide off-target effect through stringent PAM recognition
Zhou, J., Chen, P., Wang, H., Liu, H., Li, Y., Zhang, Y., Wu, Y., Paek, C., Sun, Z., Lei, J., et al. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.10.010 · Cited by 44
Controllable genome editing with split-engineered base editors
Berríos, K. N., Evitt, N. H., DeWeerd, R. A., Ren, D., Luo, M., Barka, A., Wang, T., Bartman, C., Lan, Y., Green, A. M., et al. (2021) · Nature Chemical Biology · doi:10.1038/s41589-021-00880-w · Cited by 44
CRISPR Gene Editing of Human Primary NK and T Cells for Cancer Immunotherapy
Elmas, E., Saljoughian, N., Pereira, M. D. S. F., Tullius, B. P., Sorathia, K., Nakkula, R. J., Lee, D. A., & Kararoudi, M. N. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.834002 · Cited by 47
TAPE-seq is a cell-based method for predicting genome-wide off-target effects of prime editor
Kwon, J., Kim, M., Bae, S.-M., Jo, A., Kim, Y.-H., & Lee, J. K. (2022) · Nature Communications · doi:10.1038/s41467-022-35743-y · Cited by 45
An engineered Cas12i nuclease that is an efficient genome editing tool in animals and plants
Duan, Z., Liang, Y., Sun, J., Zheng, H., Lin, T., Luo, P., Wang, M., Liu, R., Chen, Y., Guo, S., et al. (2024) · The Innovation · doi:10.1016/j.xinn.2024.100564 · Cited by 44
PAM-flexible Engineered FnCas9 variants for robust and ultra-precise genome editing and diagnostics
Acharya, S., Ansari, A. H., Das, P. K., Hirano, S., Aich, M., Rauthan, R., Mahato, S., Maddileti, S., Sarkar, S., Kumar, M., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49233-w · Cited by 47
Genome-wide CRISPR guide RNA design and specificity analysis with GuideScan2
Schmidt, H., Zhang, M., Chakarov, D., Bansal, V., Mourelatos, H. A., Rivera, F. J. S., Lowe, S. W., Ventura, A., Leslie, C. S., & Pritykin, Y. (2025) · Genome biology · doi:10.1186/s13059-025-03488-8 · Cited by 48
Conformational regulation of CRISPR-associated nucleases
Jackson, R. N., van Erp, P. B. G., Sternberg, S. H., & Wiedenheft, B. (2017) · Current Opinion in Microbiology · doi:10.1016/j.mib.2017.05.010 · Cited by 48
Nadakuduti, S. S., Starker, C. G., Ko, D. K., Jayakody, T. B., Buell, C. R., Voytas, D. F., & Douches, D. S. (2019) · Frontiers in Plant Science · doi:10.3389/fpls.2019.00110 · Cited by 44
Booth, D. S., & King, N. (2020) · eLife · doi:10.7554/elife.56193 · Cited by 44
Technologies and Computational Analysis Strategies for CRISPR Applications
Clement, K., Hsu, J. Y., Canver, M. C., Joung, J. K., & Pinello, L. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.06.012 · Cited by 45
Self-citationEvaluation of Homology-Independent CRISPR-Cas9 Off-Target Assessment Methods
Chaudhari, H. G., Penterman, J. N., Whitton, H. J., Spencer, S. J., Flanagan, N., Zhang, M. C. L., Huang, E., Khedkar, A. S., Toomey, J. M., Shearer, C. A., et al. (2020) · The CRISPR Journal · doi:10.1089/crispr.2020.0053 · Cited by 45
Hesami, M., Yoosefzadeh-Najafabadi, M., Adamek, K., Torkamaneh, D., & Jones, A. M. P. (2021) · Molecules · doi:10.3390/molecules26072053 · Cited by 44
Analysis of off-target effects in CRISPR-based gene drives in the human malaria mosquito
Garrood, W. T., Kranjc, N., Petri, K., Kim, D. Y., Guo, J. A., Hammond, A., Morianou, I., Pattanayak, V., Joung, J. K., Crisanti, A., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2004838117 · Cited by 46
Self-citationGene therapy for Fabry disease: Progress, challenges, and outlooks on gene-editing
Domm, J. M., Wootton, S. K., Medin, J. A., & West, M. L. (2021) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2021.07.006 · Cited by 45
FrCas9 is a CRISPR/Cas9 system with high editing efficiency and fidelity
Cui, Z., Tian, R., Huang, Z., Jin, Z., Li, L., Liu, J., Huang, Z., Xie, H., Liu, D., Mo, H., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29089-8 · Cited by 46
Bolsoni, J., Liu, D. X., Mohabatpour, F., Ebner, R., Sadhnani, G., Tafech, B., Leung, J., Shanta, S. R., An, K., Morin, T., et al. (2023) · ACS Nano · doi:10.1021/acsnano.3c08644 · Cited by 45
Rational design of a SOCS1-edited tumor-infiltrating lymphocyte therapy using CRISPR/Cas9 screens
Schlabach, M. R., Lin, S., Collester, Z. R., Wrocklage, C., Shenker, S., Calnan, C., Xu, T., Gannon, H., Williams, L. J., Thompson, F., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci163096 · Cited by 44
Genome editing and the next generation of antiviral therapy
Stone, D., Niyonzima, N., & Jerome, K. R. (2016) · Human Genetics · doi:10.1007/s00439-016-1686-2 · Cited by 44
A CRISPR/Cas9-based method and primer design tool for seamless genome editing in fission yeast
Rodríguez‐López, M., Cotobal, C., Fernández-Sánchez, O., Bravo, N. B., Oktriani, R., Abendroth, H., Uka, D., Hoti, M., Wang, J., Zaratiegui, M., et al. (2017) · Wellcome Open Research · doi:10.12688/wellcomeopenres.10038.3 · Cited by 43
Personalised genome editing – The future for corneal dystrophies
Moore, T., Christie, K. A., Marshall, J., & Nesbit, M. A. (2018) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.01.004 · Cited by 44
Low incidence of SNVs and indels in trio genomes of Cas9-mediated multiplex edited sheep
Wang, X., Liu, J., Niu, Y., Li, Y., Zhou, S., Li, C., Ma, B., Kou, Q., Petersen, B., Sonstegard, T. S., et al. (2018) · BMC Genomics · doi:10.1186/s12864-018-4712-z · Cited by 43
Making ends meet: targeted integration of DNA fragments by genome editing
Yamamoto, Y., & Gerbi, S. A. (2018) · Chromosoma · doi:10.1007/s00412-018-0677-6 · Cited by 49
Shape selective bifacial recognition of double helical DNA
Thadke, S. A., Hridya, V. M., Perera, J. D. R., Gil, R. R., Mukherjee, A., & Ly, D. H. (2018) · Communications Chemistry · doi:10.1038/s42004-018-0080-5 · Cited by 45
Genome Editing for Mucopolysaccharidoses
Poletto, É., Baldo, G., & Gomez‐Ospina, N. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21020500 · Cited by 45
Advances in genome editing for genetic hearing loss
Ding, N., Lee, S., Lieber-Kotz, M., Yang, J., & Gao, X. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.05.001 · Cited by 43
Genome-wide detection of DNA double-strand breaks by in-suspension BLISS
Bouwman, B. A. M., Agostini, F., Garnerone, S., Petrosino, G., Gothe, H. J., Sayols, S., Moor, A. E., Itzkovitz, S., Bienko, M., Roukos, V., et al. (2020) · Nature Protocols · doi:10.1038/s41596-020-0397-2 · Cited by 43
Engineered Cas12i2 is a versatile high-efficiency platform for therapeutic genome editing
McGaw, C., Garrity, A. J., Munoz, G., Haswell, J. R., Sengupta, S., Keston-Smith, E., Hunnewell, P., Ornstein, A., Bose, M., Wessells, Q. N., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30465-7 · Cited by 43
Kulcsár, P. I., Tálas, A., Ligeti, Z., Krausz, S. L., & Welker, E. (2022) · Nature Communications · doi:10.1038/s41467-022-34527-8 · Cited by 46
Cromer, M. K., Majeti, K. R., Rettig, G. R., Murugan, K., Kurgan, G. L., Bode, N. M., Hampton, J. P., Vakulskas, C. A., Behlke, M. A., & Porteus, M. H. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.02.011 · Cited by 42
Massively targeted evaluation of therapeutic CRISPR off-targets in cells
Pan, X., Qu, K., Yuan, H., Xiang, X., Anthon, C., Pashkova, L., Liang, X., Han, P., Corsi, G. I., Xu, F., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31543-6 · Cited by 42
Rational design of a compact CRISPR-Cas9 activator for AAV-mediated delivery
Vora, S., Cheng, J., Xiao, R., VanDusen, N. J., Quintino, L., Pu, W. T., Vandenberghe, L. H., Chavez, A., & Church, G. (2018) · doi:10.1101/298620 · Cited by 42
Building CRISPR Gene Therapies for the Central Nervous System
Salomonsson, S. E., & Clelland, C. D. (2024) · JAMA Neurology · doi:10.1001/jamaneurol.2023.4983 · Cited by 42
Fortin, J., Tan, J., Gascoigne, K. E., Haverty, P. M., Forrest, W. F., Costa, M. R., & Martin, S. E. (2019) · Genome biology · doi:10.1186/s13059-019-1621-7 · Cited by 42
CRISPR RNA-guided autonomous delivery of Cas9
Wilkinson, R. A., Martin, C. D., Nemudryi, A. A., & Wiedenheft, B. (2018) · Nature Structural & Molecular Biology · doi:10.1038/s41594-018-0173-y · Cited by 43
Predicting double-strand DNA breaks using epigenome marks or DNA at kilobase resolution
Mourad, R., Ginalski, K., Legube, G., & Cuvier, O. (2018) · Genome biology · doi:10.1186/s13059-018-1411-7 · Cited by 46
Systematic in vitro profiling of off-target affinity, cleavage and efficiency for CRISPR enzymes
Zhang, L., Rube, H. T., Vakulskas, C. A., Behlke, M. A., Bussemaker, H. J., & Pufall, M. A. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa231 · Cited by 45
GOTI, a method to identify genome-wide off-target effects of genome editing in mouse embryos
Zuo, E., Sun, Y., Wu, W., Yuan, T., Ying, W., Sun, H., Yuan, L., Steinmetz, L. M., Li, Y., & Yang, H. (2020) · Nature Protocols · doi:10.1038/s41596-020-0361-1 · Cited by 43
Amit, I., Iancu, O., Levy-Jurgenson, A., Kurgan, G., McNeill, M., Rettig, G. R., Allen, D. G., Breier, D., Haim, N. B., Wang, Y., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22417-4 · Cited by 43
Bodai, Z., Bishop, A. L., Gantz, V. M., & Komor, A. C. (2022) · Nature Communications · doi:10.1038/s41467-022-29989-9 · Cited by 44
Battling CRISPR-Cas9 off-target genome editing
Li, D., Zhou, H., & Zeng, X. (2019) · Cell Biology and Toxicology · doi:10.1007/s10565-019-09485-5 · Cited by 45
Petri, K., Kim, D. Y., Sasaki, K. E., Canver, M. C., Wang, X., Shah, H., Lee, H., Horng, J. E., Clement, K., Iyer, S., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.04.05.438458 · Cited by 44
Self-citationGenome-editing strategies for treating human retinal degenerations
Quinn, J., Musa, A., Kantor, A., McClements, M. E., Cehajic-Kapetanovic, J., MacLaren, R. E., & Xue, K. (2021) · Human Gene Therapy · doi:10.1089/hum.2020.231 · Cited by 41
The AAV-mediated and RNA-guided CRISPR/Cas9 system for gene therapy of DMD and BMD
Wang, J.-Z., Wu, P., Shi, Z.-M., Xu, Y.-L., & Liu, Z.-J. (2017) · Brain and Development · doi:10.1016/j.braindev.2017.03.024 · Cited by 41
Paving the way towards precise and safe CRISPR genome editing
Śledziński, P., Dabrowska, M., Nowaczyk, M., & Olejniczak, M. (2021) · Biotechnology Advances · doi:10.1016/j.biotechadv.2021.107737 · Cited by 43
CRISPR/Cas9 as a therapeutic tool for triple negative breast cancer: from bench to clinics
Tiwari, P. K., Ko, T.-H., Dubey, R., Chouhan, M., Tsai, L.-W., Singh, H. N., Chaubey, K. K., Dayal, D., Chiang, C., & Kumar, S. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1214489 · Cited by 42
Engineering IscB to develop highly efficient miniature editing tools in mammalian cells and embryos
Xue, N., Hong, D., Zhang, D., Wang, Q., Zhang, S., Yang, L., Chen, X., Li, Y., Han, H., Hu, C., et al. (2024) · Molecular Cell · doi:10.1016/j.molcel.2024.07.007 · Cited by 45
Effective genome editing with an enhanced ISDra2 TnpB system and deep learning-predicted ωRNAs
Marquart, K. F., Mathis, N., Mollaysa, A., Müller, S., Kissling, L., Rothgangl, T., Schmidheini, L., Kulcsár, P. I., Allam, A., Kaufmann, M. M., et al. (2024) · Nature Methods · doi:10.1038/s41592-024-02418-z · Cited by 41
Minimizing off-Target Mutagenesis Risks Caused by Programmable Nucleases
Ishida, K., Gee, P., & Hotta, A. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161024751 · Cited by 41
Novel Genome-Editing Tools to Model and Correct Primary Immunodeficiencies
de Bruin, L. M. O., Volpi, S., & Musunuru, K. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00250 · Cited by 44
Genome engineering: Drosophila melanogaster and beyond
Venken, K. J. T., Sarrion‐Perdigones, A., Vandeventer, P. J., Abel, N. S., Christiansen, A. E., & Hoffman, K. L. (2015) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.214 · Cited by 43
Progress With Developing Use of Gene Editing To Cure Chronic Infection With Hepatitis B Virus
Ely, A., Moyo, B., & Arbuthnot, P. B. (2016) · Molecular Therapy · doi:10.1038/mt.2016.43 · Cited by 41
CRISPR-Cas9 as a Powerful Tool for Efficient Creation of Oncolytic Viruses
Yuan, M., Webb, E., Lemoine, N. R., & Wang, Y. (2016) · Viruses · doi:10.3390/v8030072 · Cited by 43
Rivera-Torres, N., Banas, K. H., Bialk, P. A., Bloh, K. M., & Kmiec, E. B. (2017) · PLoS ONE · doi:10.1371/journal.pone.0169350 · Cited by 41
Du, J., Yin, N., Xie, T., Zheng, Y., Xia, N., Shang, J., Chen, F., Zhang, H., Yu, J., & Liu, F. (2018) · DNA repair · doi:10.1016/j.dnarep.2018.09.002 · Cited by 41
Therapeutic genome editing in cardiovascular diseases
Nishiga, M., Qi, L. S., & Wu, J. C. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.02.003 · Cited by 42
Knockout of the HMG domain of the porcine SRY gene causes sex reversal in gene-edited pigs
Kurtz, S., Lucas‐Hahn, A., Schlegelberger, B., Göhring, G., Niemann, H., Mettenleiter, T. C., & Petersen, B. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2008743118 · Cited by 41
Kim, D., Kang, B., & Kim, J. (2021) · Nature Protocols · doi:10.1038/s41596-020-00453-6 · Cited by 44
GUIDEseq: a bioconductor package to analyze GUIDE-Seq datasets for CRISPR-Cas nucleases
Zhu, L. J., Lawrence, M., Gupta, A., Pagès, H., Küçükural, A., Garber, M. G., & Wolfe, S. A. (2017) · BMC Genomics · doi:10.1186/s12864-017-3746-y · Cited by 42
Niu, R., Peng, J., Zhang, Z., & Shang, X. (2021) · Genes · doi:10.3390/genes12121878 · Cited by 43
Jamal, M., Khan, F. A., Lin, D., Habib, Z., Dai, J., & Cao, G. (2016) · Current Issues in Molecular Biology · doi:10.21775/cimb.020.001 · Cited by 41
Mapping the precision of genome editing
Gabriel, R., Kalle, C. V., & Schmidt, M. (2015) · Nature Biotechnology · doi:10.1038/nbt.3142 · Cited by 40
Shen, H. M., McHale, C. M., Smith, M. T., & Zhang, L. (2015) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2015.01.002 · Cited by 40
CRISPR‐Cas9 systems: versatile cancer modelling platforms and promising therapeutic strategies
Wen, W., Yuan, Z., Ma, S., Jiang, X., & Yuan, D. (2015) · International Journal of Cancer · doi:10.1002/ijc.29626 · Cited by 41
A more efficient CRISPR-Cas12a variant derived from Lachnospiraceae bacterium MA2020
Tran, M. H., Park, H., Nobles, C. L., Karunadharma, P. P., Pan, L., Zhong, G., Wang, H., He, W., Ou, T., Crynen, G. C., et al. (2021) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2021.02.012 · Cited by 41
Review of applications of CRISPR-Cas9 gene-editing technology in cancer research
Zhao, Z., Li, C., Tong, F., Deng, J., Huang, G., & Sang, Y. (2021) · Biological Procedures Online · doi:10.1186/s12575-021-00151-x · Cited by 42
Eslami-Mossallam, B., Klein, M., van der Smagt, C. P., van der Sanden, K., Jones, S. K., Hawkins, J. A., Finkelstein, I. J., & Depken, M. (2022) · Nature Communications · doi:10.1038/s41467-022-28994-2 · Cited by 40
Distinct mechanisms for genomic attachment of the 5′ and 3′ ends of Agrobacterium T-DNA in plants
Kralemann, L. E. M., de Pater, S., Shen, H., Kloet, S. L., van Schendel, R., Hooykaas, P. J. J., & Tijsterman, M. (2022) · Nature Plants · doi:10.1038/s41477-022-01147-5 · Cited by 40
Zhang, Z., Tang, C. Y., Dong, Y., Zhang, J., Yuan, T., & Li, X. (2017) · Journal of Cancer · doi:10.7150/jca.22113 · Cited by 40
Myoediting: Toward Prevention of Muscular Dystrophy by Therapeutic Genome Editing
Zhang, Y., Long, C., Bassel‐Duby, R., & Olson, E. N. (2018) · Physiological Reviews · doi:10.1152/physrev.00046.2017 · Cited by 42
Reprogramming the anti-tumor immune response via CRISPR genetic and epigenetic editing
Alves, E., Taifour, S., Dolcetti, R., Chee, J., Nowak, A. K., Gaudieri, S., & Blancafort, P. (2021) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2021.04.009 · Cited by 40
Whole-brain in vivo base editing reverses behavioral changes in Mef2c-mutant mice
Li, W.-K., Zhang, S.-Q., Peng, W., Shi, Y., Yuan, B., Yuan, Y., Xue, Z., Wang, J., Han, W., Chen, Z., et al. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01499-x · Cited by 40
A Toolkit of CRISPR-Based Genome Editing Systems in Drosophila
Jiang, X., Ren, X., Sun, J., Wang, X., Qiao, H., Xu, B., Liu, L., & Ni, J. (2015) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2015.02.007 · Cited by 39
Diving into marine genomics with CRISPR/Cas9 systems
Momose, T., & Concordet, J. (2016) · Marine Genomics · doi:10.1016/j.margen.2016.10.003 · Cited by 40
Genome-wide Specificity of Highly Efficient TALENs and CRISPR/Cas9 for T Cell Receptor Modification
Knipping, F., Osborn, M. J., Petri, K., Tolar, J., Glimm, H., Kalle, C. V., Schmidt, M., & Gabriel, R. (2017) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2017.01.005 · Cited by 41
CRISPR-Cap: multiplexed double-stranded DNA enrichment based on the CRISPR system
Lee, J., Lim, H., Jang, H. S., Hwang, B., Lee, J. H., Cho, J., Lee, J. H., & Bang, D. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky820 · Cited by 39
Mitsui, R., Yamada, R., & Ogino, H. (2019) · World Journal of Microbiology and Biotechnology · doi:10.1007/s11274-019-2688-8 · Cited by 39
Kordon-Kiszala, M., Zarębski, M., Solarczyk, K. J., Ma, H., Pederson, T., & Dobrucki, J. W. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz1118 · Cited by 41
Epigenetic Footprints of CRISPR/Cas9-Mediated Genome Editing in Plants
Lee, J. H., Mazarei, M., Pfotenhauer, A. C., Dorrough, A. B., Poindexter, M. R., Hewezi, T., Lenaghan, S. C., Graham, D. E., & Stewart, C. N. (2020) · Frontiers in Plant Science · doi:10.3389/fpls.2019.01720 · Cited by 39
Genetics in Light of Transcriptional Adaptation
Kontarakis, Z., & Stainier, D. Y. R. (2020) · Trends in Genetics · doi:10.1016/j.tig.2020.08.008 · Cited by 41
Hematopoietic Stem Cell-Targeted Gene-Addition and Gene-Editing Strategies for β-hemoglobinopathies
Drysdale, C. M., Nassehi, T., Gamer, J., Yapundich, M., Tisdale, J. F., & Uchida, N. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.01.001 · Cited by 39
CD7-deleted hematopoietic stem cells can restore immunity after CAR T cell therapy
Kim, M. Y., Cooper, M. L., Jacobs, M. T., Ritchey, J., Hollaway, J., Fehniger, T. A., & DiPersio, J. F. (2021) · JCI Insight · doi:10.1172/jci.insight.149819 · Cited by 40
Recent Advancements in DNA Damage–Transcription Crosstalk and High-Resolution Mapping of DNA Breaks
Vitelli, V., Galbiati, A., Iannelli, F., Pessina, F., Sharma, S., & di Fagagna, F. D. (2017) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-091416-035314 · Cited by 41
CRISPR–Cas9 gene editing induced complex on-target outcomes in human cells
Wen, W., & Zhang, X. (2022) · Experimental Hematology · doi:10.1016/j.exphem.2022.03.002 · Cited by 41
Massively parallel analysis of single-molecule dynamics on next-generation sequencing chips
Rivera, J. A., Mao, G., Владимирович, С. А., Panfilov, M., Hou, Q., Lindell, M., Chanez, C., Ritort, F., Jínek, M., & Deindl, S. (2024) · Science · doi:10.1126/science.adn5371 · Cited by 40
Overview of guide RNA design tools for CRISPR-Cas9 genome editing technology
Zhu, L. J. (2015) · Frontiers in Biology · doi:10.1007/s11515-015-1366-y · Cited by 38
Simple, Efficient CRISPR-Cas9-Mediated Gene Editing in Mice: Strategies and Methods
Low, B. E., Kutny, P. M., & Wiles, M. V. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-3661-8_2 · Cited by 38
Synergizing CRISPR/Cas9 off-target predictions for ensemble insights and practical applications
Zhang, S., Li, X., Lin, Q., & Wong, K. (2018) · Bioinformatics · doi:10.1093/bioinformatics/bty748 · Cited by 40
Computational Analysis Concerning the Impact of DNA Accessibility on CRISPR-Cas9 Cleavage Efficiency
Chung, C.-H., Allen, A. G., Sullivan, N. T., Atkins, A., Nonnemacher, M. R., Wigdahl, B. L., & Dampier, W. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.10.008 · Cited by 40
A Tale of Two Moieties: Rapidly Evolving CRISPR/Cas-Based Genome Editing
Yang, L. C., & Chen, J. (2020) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.06.003 · Cited by 38
Lee, B., Lozano, R. J., & Dunbar, C. E. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.09.001 · Cited by 39
Development of a versatile nuclease prime editor with upgraded precision
Li, X., Zhang, G., Huang, S., Liu, Y., Tang, J., Zhong, M., Wang, X., Sun, W., Yao, Y., Ji, Q., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-35870-0 · Cited by 39
Negative DNA supercoiling induces genome-wide Cas9 off-target activity
Newton, M. D., Losito, M., Smith, Q. M., Parnandi, N., Taylor, B. J., Akçakaya, P., Maresca, M., van Eijk, P., Reed, S. H., Boulton, S. J., et al. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.09.008 · Cited by 41
Musunuru, K. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.10.002 · Cited by 38
Tycko, J., Barrera, L. A., Huston, N. C., Friedland, A. E., Wu, X., Gootenberg, J. S., Abudayyeh, O. O., Myer, V. E., Wilson, C. J., & Hsu, P. D. (2018) · Nature Communications · doi:10.1038/s41467-018-05391-2 · Cited by 38
crisprSQL: a novel database platform for CRISPR/Cas off-target cleavage assays
Störtz, F., & Minary, P. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkaa885 · Cited by 37
Hu, R., Guo, C., Liu, C., Zhang, Q., Zhang, X., Chen, Y., & Liu, Y. (2024) · Analytical Chemistry · doi:10.1021/acs.analchem.4c02726 · Cited by 37
Efficient Precision Genome Editing in iPSCs via Genetic Co-targeting with Selection
Mitzelfelt, K. A., McDermott‐Roe, C., Grzybowski, M. N., Marquez, M., Kuo, C.-T., Riedel, M. J., Lai, S., Choi, M. J., Kolander, K. D., Helbling, D. C., et al. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.01.021 · Cited by 37
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
