Correction of a genetic disease in mouse via use of CRISPR-Cas9
Open accessAbstract
The CRISPR-Cas9 system has been employed to generate mutant alleles in a range of different organisms. However, so far there have not been reports of use of this system for efficient correction of a genetic disease. Here we show that mice with a dominant mutation in Crygc gene that causes cataracts could be rescued by coinjection into zygotes of Cas9 mRNA and a single-guide RNA (sgRNA) targeting the mutant allele. Correction occurred via homology-directed repair (HDR) based on an exogenously supplied oligonucleotide or the endogenous WT allele, with only rare evidence of off-target modifications. The resulting mice were fertile and able to transmit the corrected allele to their progeny. Thus, our study provides proof of principle for use of the CRISPR-Cas9 system to correct genetic disease.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Several groups have demonstrated in vitro correction of genetic disease genes including CFTR, Crygc and DMD in organoids or mouse zygotes.
“Several groups have also demonstrated in vitro correction of genetic disease genes including CFTR (cystic fibrosis)9, Crygc (cataracts)10 and DMD (Duchenne muscular dystrophy)11 in organoids or mouse zygotes.”
From Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo (2016) · cites this paper as [10]
CRISPR/Cas9 system holds tremendous promise for gene therapy and can correct causal mutations in the original genome and rescue disease phenotypes of monogenic disorders permanently.
“Furthermore, CRISPR/Cas9 system holds tremendous promise for gene therapy [46–51]. It can correct causal mutations in the original genome and rescue the disease phenotypes of monogenic disorders permanently, which currently represents the most translatable field in CRISPR/Cas9-mediated disease therapy.”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [47]
CRISPR-Cas9 genome editing has been applied to correct disease-causing mutations in mouse zygotes and human cell lines for cataract and cystic fibrosis.
“CRISPR-Cas9 genome editing has been applied to correct disease-causing mutations in mouse zygotes and human cell lines for cataract5 and cystic fibrosis6”
From Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype (2014) · cites this paper as [5]
In a mouse Crygc cataract model, germline manipulation with CRISPR-Cas9 corrected both the mutant gene and cataract phenotype in part of the offspring.
“In such a mouse model, germline-manipulation with CRISPR-Cas9 system was capable of correcting both the mutant gene and cataract phenotype in part of offsprings.”
From CRISPR-Cas9: a new and promising player in gene therapy (2015) · cites this paper as [30]
Of six offspring undergoing NHEJ, two were free of cataract due to coincidental frameshift restoration, while four remained cataract phenotype.
“Interestingly, however, of the six offsprings undergoing NHEJ, two were also free of cataract thanks to coincidental frameshift restoration resulting from NHEJ-induced indel mutations, while the rest four remained cataract phenotype.30”
From CRISPR-Cas9: a new and promising player in gene therapy (2015) · cites this paper as [30]
These results highlighted the importance of HDR in reliable gene corrections.
“These results highlighted the importance of HDR in reliable gene corrections.”
From CRISPR-Cas9: a new and promising player in gene therapy (2015) · cites this paper as [30]
Of 22 live offspring, 10 underwent culprit gene modifications (45.45%) either by HDR (n=4) or by NHEJ (n=6).
“Of the 22 live offsprings, 10 underwent culprit gene modifications (the editing efficiency is 45.45%) either by HDR (n=4) (figure 1C left) or by NHEJ (n=6) (figure 1C right).”
From CRISPR-Cas9: a new and promising player in gene therapy (2015) · cites this paper as [30]
Zygote manipulation can only rescue part of the offspring in an unpredictable manner.
“However, as demonstrated in this study, zygote manipulation can only rescue part of the offsprings in an unpredictable manner.”
From CRISPR-Cas9: a new and promising player in gene therapy (2015) · cites this paper as [30]
All four offspring undergoing HDR were free of cataract due to HDR-mediated gene corrections.
“As expected, all of the four offsprings undergoing HDR were free of cataract due to HDR-mediated gene corrections.”
From CRISPR-Cas9: a new and promising player in gene therapy (2015) · cites this paper as [30]
Among mice genetically edited by CRISPR-Cas9, all HDR-mediated editing corrected causative gene defects and rescued disease phenotype, while only a small part of NHEJ-mediated editing had the corrective effect.
“As shown in the study by Wu et al 30 among mice genetically edited by CRISPR-Cas9, all HDR-mediated editing corrected the causative gene defects and rescued disease phenotype while only a small part of NHEJ-mediated editing had the corrective effect.”
From CRISPR-Cas9: a new and promising player in gene therapy (2015) · cites this paper as [30]
Cites
Multiplex Genome Engineering Using CRISPR/Cas Systems
Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., et al. (2013) · Science · doi:10.1126/science.1231143 · Cited by 15,339 · see citing works
RNA-Guided Human Genome Engineering via Cas9
Mali, P., Yang, L., Esvelt, K. M., Aach, J., Guell, M., DiCarlo, J. E., Norville, J. E., & Church, G. M. (2013) · Science · doi:10.1126/science.1232033 · Cited by 9,210 · see citing works
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 · see citing works
ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering
Gaj, T., Gersbach, C. A., & Barbas, C. F. (2013) · Trends in Biotechnology · doi:10.1016/j.tibtech.2013.04.004 · Cited by 3,820 · see citing works
Wang, H., Yang, H., Shivalila, C. S., Dawlaty, M. M., Cheng, A. W., Zhang, F., & Jaenisch, R. (2013) · Cell · doi:10.1016/j.cell.2013.04.025 · Cited by 3,495 · see citing works
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 · see citing works
Efficient genome editing in zebrafish using a CRISPR-Cas system
Hwang, W. Y., Fu, Y., Reyon, D., Maeder, M. L., Tsai, S. Q., Sander, J. D., Peterson, R. T., Yeh, J.-R. J., & Joung, J. K. (2013) · Nature Biotechnology · doi:10.1038/nbt.2501 · Cited by 2,937 · see citing works
RNA-programmed genome editing in human cells
Jinek, M., East, A., Cheng, A., Lin, S., Ma, E., & Doudna, J. (2013) · eLife · doi:10.7554/elife.00471 · Cited by 2,098 · see citing works
Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease
Cho, S. W., Kim, S., Kim, J. M., & Kim, J.-S. (2013) · Nature Biotechnology · doi:10.1038/nbt.2507 · Cited by 1,863 · see citing works
Yang, H., Wang, H., Shivalila, C. S., Cheng, A. W., Shi, L., & Jaenisch, R. (2013) · Cell · doi:10.1016/j.cell.2013.08.022 · Cited by 1,596 · see citing works
Pattanayak, V., Lin, S., Guilinger, J. P., Ma, E., Doudna, J. A., & Liu, D. R. (2013) · Nature Biotechnology · doi:10.1038/nbt.2673 · Cited by 1,487 · see citing works
Efficient multiplex biallelic zebrafish genome editing using a CRISPR nuclease system
Jao, L.-E., Wente, S. R., & Chen, W. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1308335110 · Cited by 1,261 · see citing works
Engineering the Caenorhabditis elegans genome using Cas9-triggered homologous recombination
Dickinson, D. J., Ward, J. D., Reiner, D. J., & Goldstein, B. (2013) · Nature Methods · doi:10.1038/nmeth.2641 · Cited by 915 · see citing works
Heritable genome editing in C. elegans via a CRISPR-Cas9 system
Friedland, A. E., Tzur, Y. B., Esvelt, K. M., Colaiácovo, M. P., Church, G. M., & Calarco, J. A. (2013) · Nature Methods · doi:10.1038/nmeth.2532 · Cited by 899 · see citing works
Genome editing with RNA-guided Cas9 nuclease in Zebrafish embryos
Chang, N., Sun, C., Gao, L., Zhu, D., Xu, X., Zhu, X., Xiong, J., & Xi, J. (2013) · Cell Research · doi:10.1038/cr.2013.45 · Cited by 819 · see citing works
Heritable gene targeting in the mouse and rat using a CRISPR-Cas system
Li, D., Qiu, Z., Shao, Y., Chen, Y., Guan, Y., Liu, M., Li, Y., Wang, L., Wang, L., Lu, X., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2661 · Cited by 639 · see citing works
Generation of gene-modified mice via Cas9/RNA-mediated gene targeting
Shen, B., Zhang, J., Wu, H., Wang, J., Ma, K., Li, Z., Zhang, X., Zhang, P., & Huang, X. (2013) · Cell Research · doi:10.1038/cr.2013.46 · Cited by 556 · see citing works
Li, W., Teng, F., Li, T., & Zhou, Q. (2013) · Nature Biotechnology · doi:10.1038/nbt.2652 · Cited by 422 · see citing works
Highly Efficient Genome Modifications Mediated by CRISPR/Cas9 in Drosophila
Yu, Z., Ren, M., Wang, Z., Zhang, B., Rong, Y. S., Jiao, R., & Gao, G. (2013) · Genetics · doi:10.1534/genetics.113.153825 · Cited by 339 · see citing works
A 1-bp deletion in the γC-crystallin leads to dominant cataracts in mice
Zhao, L., Li, K., Bao, S., Zhou, Y., Liang, Y., Zhao, G., Chen, Y., & Xiao, J. (2010) · Mammalian Genome · doi:10.1007/s00335-010-9275-5 · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The new frontier of genome engineering with CRISPR-Cas9
Doudna, J. A., & Charpentier, E. (2014) · Science · doi:10.1126/science.1258096 · Cited by 7,062 · see citing works
“A dominant mutation in the Crygc gene responsible for cataracts was successfully corrected in mice (103).”
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 · see citing works
“, 2014), to engineer isogenic ES and iPS cell disease models with specific mutations introduced or corrected, respectively, or in vivo and ex vivo gene correction (Schwank et al., 2013; Wu et al., 2013).”
Ma, X., Zhang, Q., Zhu, Q., Liu, W., Chen, Y., Qiu, R., Wang, B., Yang, Z., Li, H., Lin, Y., et al. (2015) · Molecular Plant · doi:10.1016/j.molp.2015.04.007 · Cited by 2,369 · see citing works
“A previous report showed that CRISPR/Cas9-induced DSB in a mutated gene in mice could be corrected to wild-type through the HR mechanism, also termed homology-directed repair (HDR), with the endogenous wild-type allele as the template (Wu et al., 2013).”
BackgroundTherapeutic genome editing: prospects and challenges
Cox, D. B. T., Platt, R. J., & Zhang, F. (2015) · Nature Medicine · doi:10.1038/nm.3793 · Cited by 1,336 · see citing works
Delivering CRISPR: a review of the challenges and approaches
Lino, C. A., Harper, J. C., Carney, J. P., & Timlin, J. A. (2018) · Drug Delivery · doi:10.1080/10717544.2018.1474964 · Cited by 1,185 · see citing works
“, 2014), correction of a cataract-causing mutation in mice (Wu et al., 2013), and correction of a Duchenne muscular dystrophy (DMD)-causing mutation in mice (Long et al.”
BackgroundCRISPR/Cas9 in Genome Editing and Beyond
Wang, H., Russa, M. F. L., & Qi, L. S. (2016) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014607 · Cited by 1,165 · see citing works
“A partial list includes the Fah gene in hereditary tyrosinemia (125), Dystrophin in Duchenne’s muscular dystrophy (126, 133), Crygc in cataracts (127, 128), CTFR in cystic fibrosis (129), HBB in β-thalassemia”
BackgroundCRISPR/Cas9-mediated gene editing in human tripronuclear zygotes
Liang, P., Xu, Y., Zhang, X., Ding, C., Huang, R., Zhang, Z., Lv, J., Xie, X., Chen, Y., Li, Y., et al. (2015) · Protein & Cell · doi:10.1007/s13238-015-0153-5 · Cited by 1,135 · see citing works
“…et al., 2013; Hsu et al., 2014; Hwang et al., 2013; Ikmi et al., 2014; Irion et al., 2014; Jinek et al., 2013; Li et al., 2013a; Li et al., 2013b; Long et al., 2014; Ma et al., 2014; Mali et al., 2013c; Niu et al., 2014; Smith et al., 2014a; Wu et al., 2013; Wu et al., 2014b; Yang et al., 2013).”
BackgroundInfluentialMaruyama, T., Dougan, S. K., Truttmann, M. C., Bilate, A. M., Ingram, J. R., & Ploegh, H. L. (2015) · Nature Biotechnology · doi:10.1038/nbt.3190 · Cited by 1,137 · see citing works
Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery
Kowalski, P. S., Rudra, A., Miao, L., & Anderson, D. G. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.02.012 · Cited by 1,127 · see citing works
“147 – 149 These approaches reduce the risk of off-target genetic perturbations, as only the pre-selected and correctly edited cells can be implanted into patients.”
CRISPR-Based Technologies for the Manipulation of Eukaryotic Genomes
Komor, A. C., Badran, A. H., & Liu, D. R. (2016) · Cell · doi:10.1016/j.cell.2016.10.044 · Cited by 1,011 · see citing works
Genome-wide binding of the CRISPR endonuclease Cas9 in mammalian cells
Wu, X., Scott, D. A., Kriz, A. J., Chiu, A. C., Hsu, P. D., Dadon, D. B., Cheng, A. W., Trevino, A. E., Konermann, S., Chen, S., et al. (2014) · Nature Biotechnology · doi:10.1038/nbt.2889 · Cited by 944 · see citing works
“The simplicity of targeting any locus with a single protein and a programmable sgRNA has quickly led to widespread use of Cas9 11,12 in applications such as genome editing 7,8,13–16 , disease gene repair 17,18 and knock-in of specific tags 8,19 .”
Applications of CRISPR technologies in research and beyond
Barrangou, R., & Doudna, J. A. (2016) · Nature Biotechnology · doi:10.1038/nbt.3659 · Cited by 1,005 · see citing works
Correction of a pathogenic gene mutation in human embryos
Ma, H., Marti-Gutierrez, N., Park, S.-W., Wu, J., Lee, Y., Suzuki, K., Koski, A., Ji, D., Hayama, T., Ahmed, R., et al. (2017) · Nature · doi:10.1038/nature23305 · Cited by 969 · see citing works
Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype
Yin, H., Xue, W., Chen, S., Bogorad, R. L., Benedetti, E., Grompe, M., Koteliansky, V., Sharp, P. A., Jacks, T., & Anderson, D. G. (2014) · Nature Biotechnology · doi:10.1038/nbt.2884 · Cited by 951 · see citing works
FGF/FGFR signaling in health and disease
Xie, Y., Su, N., Yang, J., Tan, Q., Huang, S., Jin, M., Ni, Z., Zhang, B., Zhang, D., Luo, F., et al. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00222-7 · Cited by 904 · see citing works
Yin, H., Song, C.-Q., Dorkin, J. R., Zhu, L. J., Li, Y., Wu, Q., Park, A., Yang, J., Suresh, S., Bizhanova, A., et al. (2016) · Nature Biotechnology · doi:10.1038/nbt.3471 · Cited by 876 · see citing works
Structure and Degradation of Circular RNAs Regulate PKR Activation in Innate Immunity
Liu, C., Li, X., Nan, F., Jiang, S., Gao, X., Guo, S.-K., Xue, W., Cui, Y., Dong, K., Ding, H., et al. (2019) · Cell · doi:10.1016/j.cell.2019.03.046 · Cited by 800 · see citing works
CRISPR-mediated direct mutation of cancer genes in the mouse liver
Xue, W., Chen, S., Yin, H., Tammela, T., Papagiannakopoulos, T., Joshi, N. S., Cai, W., Yang, G., Bronson, R., Crowley, D. G., et al. (2014) · Nature · doi:10.1038/nature13589 · Cited by 776 · see citing works
Prevention of muscular dystrophy in mice by CRISPR/Cas9–mediated editing of germline DNA
Long, C., McAnally, J. R., Shelton, J. M., Mireault, A. A., Bassel-Duby, R., & Olson, E. N. (2014) · Science · doi:10.1126/science.1254445 · Cited by 720 · see citing works
CRISPR/Cas9 therapeutics: progress and prospects
Li, T., Yang, Y., Qi, H., Cui, W., Zhang, L., Fu, X., He, X., Liu, M., Li, P., & Yu, T. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01309-7 · Cited by 770 · see citing works
“Fortunately, the chance of HDR occurring in mature cells is much lower than that of NHEJ.(68) Cas9 efficiently cleaves double-stranded DNA, but in practice, the sgRNA often mismatches with double-stranded DNA, leading to offtarget effects.”
BackgroundInfluentialGenome-editing Technologies for Gene and Cell Therapy
Maeder, M. L., & Gersbach, C. A. (2016) · Molecular Therapy · doi:10.1038/mt.2016.10 · Cited by 722 · see citing works
The CRISPR-Cas immune system: Biology, mechanisms and applications
Rath, D., Amlinger, L., Rath, A., & Lundgren, M. (2015) · Biochimie · doi:10.1016/j.biochi.2015.03.025 · Cited by 565 · see citing works
Wang, H.-X., Li, M., Lee, C. M., Chakraborty, S., Kim, H.-W., Bao, G., & Leong, K. W. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.6b00799 · Cited by 560 · see citing works
Expanding the genetic editing tool kit: ZFNs, TALENs, and CRISPR-Cas9
Gupta, R. M., & Musunuru, K. (2014) · Journal of Clinical Investigation · doi:10.1172/jci72992 · Cited by 545 · see citing works
Efficient Gene Disruption in Diverse Strains of Toxoplasma gondii Using CRISPR/CAS9
Shen, B., Brown, K. M., Lee, T. D., & Sibley, L. D. (2014) · mBio · doi:10.1128/mbio.01114-14 · Cited by 453 · see citing works
“CRISPR/CAS9 stimulated homologous recombination has been used to correct genetic disorders in a few disease models by replacing the mutated genes with wild-type copies through homology-directed repair (30, 31).”
MethodGenome-Editing Technologies: Principles and ApplicationsPreprint
Gaj, T., Sirk, S. J., Shui, S., & Liu, J. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a023754 · Cited by 425 · see citing works
“…the rapid creation of transgenic zebrafish (Doyon et al. 2008; Sander et al. 2011a; Hwang et al. 2013), mice (Cui et al. 2011; Wang et al. 2013; Wu et al. 2013), rats (Geurts et al. 2009; Tesson et al. 2011; Li et al. 2013), monkeys (Liu et al. 2014c), and livestock (Hauschild et al. 2011;…”
BackgroundXie, S., Shen, B., Zhang, C., Huang, X., & Zhang, Y. (2014) · PLoS ONE · doi:10.1371/journal.pone.0100448 · Cited by 417 · see citing works
“An interesting report shows that the CRISPRCas9 system can be used successfully to correct a genetic disease in mice with cataracts [23].”
BackgroundNon-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities
Li, L., Hu, S., & Chen, X. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.04.031 · Cited by 415 · see citing works
Xu, Y., & Li, Z. (2020) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2020.08.031 · Cited by 424 · see citing works
Xie, F., Ye, L., Chang, J. C., Beyer, A. I., Wang, J., Muench, M. O., & Kan, Y. W. (2014) · Genome Research · doi:10.1101/gr.173427.114 · Cited by 404 · see citing works
“1526 Genome Research www.genome.org 24:1526–1533 Published by Cold Spring Harbor Laboratory Press; ISSN 1088-9051/14; www.genome.org locus in cultured cells, plants, and animals (Cradick et al. 2013; Nekrasov et al. 2013;Wu et al. 2013; Yang et al. 2013).”
BackgroundRNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges
Yu, A., Choi, Y. H., & Tu, M. (2020) · Pharmacological Reviews · doi:10.1124/pr.120.019554 · Cited by 405 · see citing works
“…et al., 2006; Ivics et al., 2014a,b; Ellis et al., 2017), CRISPR-associated proteins, or endo-nucleases (e.g., Cas9 and Cas12a) (Wang et al., 2013; Wu et al., 2013; Yin et al., 2016; Ren et al., 2017; Cromer et al., 2018; Xu et al., 2018; Gurumurthy et al., 2019) to enable genome editing or…”
BackgroundNaturally Occurring Off-Switches for CRISPR-Cas9
Pawluk, A., Amrani, N., Zhang, Y., Garcı́a, B., Hidalgo-Reyes, Y., Lee, J., Edraki, A., Shah, M. K., Sontheimer, E. J., Maxwell, K. L., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.017 · Cited by 384 · see citing works
“…gene therapy to correct inherited disease, for sequence-specific targeting of pathogens to treat infectious disease, and many other applications (Bikard et al., 2014; Ebina et al., 2013; Gomaa et al., 2014; Kaminski et al., 2016; Ousterout et al., 2015; Wu et al., 2013; Yin et al., 2014).”
Target specificity of the CRISPR‐Cas9 system
Wu, X., Kriz, A. J., & Sharp, P. A. (2014) · Quantitative Biology · doi:10.1007/s40484-014-0030-x · Cited by 373 · see citing works
“With exogenous template oligos, specific sequences such as HA-tag or GFP could be inserted into genes to label proteins [19,20], or to correct mutations in disease genes in human and mouse [21–23].”
ssODN-mediated knock-in with CRISPR-Cas for large genomic regions in zygotes
Yoshimi, K., Kunihiro, Y., Kaneko, T., Nagahora, H., Voigt, B., & Mashimo, T. (2016) · Nature Communications · doi:10.1038/ncomms10431 · Cited by 352 · see citing works
Canver, M. C., Bauer, D. E., Dass, A., Yien, Y. Y., Chung, J., Masuda, T., Maeda, T., Paw, B. H., & Orkin, S. H. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.564625 · Cited by 342 · see citing works
In vivo CRISPR editing with no detectable genome-wide off-target mutations
Akçakaya, P., Bobbin, M. L., Guo, J. A., Malagon-Lopez, J., Clement, K., Garcia, S. P., Fellows, M. D., Porritt, M. J., Firth, M. A., Carreras, A., et al. (2018) · Nature · doi:10.1038/s41586-018-0500-9 · Cited by 316 · see citing works
A Mouse Geneticist’s Practical Guide to CRISPR Applications
Singh, P., Schimenti, J. C., & Bolcun‐Filas, E. (2014) · Genetics · doi:10.1534/genetics.114.169771 · Cited by 303 · see citing works
“causing mutations and reverse the phenotypes (Wu et al. 2013; Yoshimi et al. 2014), but the biggest obstacle for therapeutic use of CRISPRs in humans would be the delivery of editing reagents for efficient allele correction in vivo or in stem cells that can be re-introduced into people.”
BackgroundDistinct Processing of lncRNAs Contributes to Non-conserved Functions in Stem Cells
Guo, C., Ma, X.-K., Xing, Y., Zheng, C.-C., Xu, Y.-F., Shan, L., Zhang, J., Wang, S., Wang, Y., Carmichael, G., et al. (2020) · Cell · doi:10.1016/j.cell.2020.03.006 · Cited by 305 · see citing works
Cloning-free CRISPR/Cas system facilitates functional cassette knock-in in mice
Aida, T., Chiyo, K., Usami, T., Ishikubo, H., Imahashi, R., Wada, Y., Tanaka, K. F., Sakuma, T., Yamamoto, T., & Tanaka, K. (2015) · Genome biology · doi:10.1186/s13059-015-0653-x · Cited by 296 · see citing works
“In addition to the generation of knock-in mice carrying complex gene cassettes, our method can be directly applied to the generation of knockout mice [23] and knock-in mice carrying single nucleotide substitutions with oligo DNA donors [5,7,8], as well as to other species [39-41] and cultured cells [22,28], and in viv…”
BackgroundMethodEuPaGDT: a web tool tailored to design CRISPR guide RNAs for eukaryotic pathogens
Peng, D., & Tarleton, R. L. (2015) · Microbial Genomics · doi:10.1099/mgen.0.000033 · Cited by 293 · see citing works
“In addition to relying on MMEJ-induced deletions to mutate specific sequences, single-stranded oligonucleotides (ssODNs) bearing homology arms bracketing gRNA-guided DSBs can be used to introduce modifications at specific target positions by homology-directed repair (HDR; Wang et al., 2013; Wu et al., 2013; Yang et al…”
MethodTALEN and CRISPR/Cas Genome Editing Systems: Tools of Discovery
Nemudryi, A. A., Valetdinova, K. R., Medvedev, S. P., & Zakian, S. M. (2014) · Acta Naturae · doi:10.32607/20758251-2014-6-3-19-40 · Cited by 284 · see citing works
Machine Learning in Genomic Medicine: A Review of Computational Problems and Data Sets
Leung, M. K. K., Delong, A., Alipanahi, B., & Frey, B. J. (2015) · Proceedings of the IEEE · doi:10.1109/jproc.2015.2494198 · Cited by 276 · see citing works
“The system has been used to control gene expression by deactivating the endonuclease domain [201], study gene functions in neural cells [202], develop synthetic biology applications [203], fix pathogenic mutations causing -thalassemia [204], and to repair cystic fibrosis transmembrane conductor receptor mutations [205…”
MethodGenome modification by CRISPR /Cas9
Ma, Y., Zhang, L., & Huang, X. (2014) · FEBS Journal · doi:10.1111/febs.13110 · Cited by 279 · see citing works
Kang, X., He, W., Huang, Y., Qian, Y., Chen, Y., Gao, X., Sun, X., & Fan, Y. (2016) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-016-0710-8 · Cited by 263 · see citing works
“causing mutations, leading to the production of healthy adult animals [8, 9].”
BackgroundAdvances in therapeutic CRISPR/Cas9 genome editing
Savić, N., & Schwank, G. (2016) · Translational Research · doi:10.1016/j.trsl.2015.09.008 · Cited by 257 · see citing works
Genome Editing with mRNA Encoding ZFN, TALEN, and Cas9
Zhang, H., Zhang, Y., & Yin, H. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.01.014 · Cited by 248 · see citing works
“For a proof of concept of potential therapeutic applications, such method can be applied to correct genetic mutations in genes in mouse zygotes as well as spermatogonial stem cells, leading to bear healthy animals.(157,158) Pigs bearing biallelic knockout have been generated in one step by an injection of Cas9 mRNA an…”
MethodWu, Y., Zhou, H., Fan, X., Zhang, Y., Zhang, M., Wang, Y., Xie, Z., Bai, M., Yin, Q., Liang, D., et al. (2015) · Cell Research · doi:10.1038/cr.2014.160 · Cited by 247 · see citing works
Artificial Virus Delivers CRISPR-Cas9 System for Genome Editing of Cells in Mice
Li, L., Song, L., Liu, X., Yang, X., Li, X., He, T., Wang, N., Yang, S., Yu, C., Yin, T., et al. (2017) · ACS Nano · doi:10.1021/acsnano.6b04261 · Cited by 244 · see citing works
CRISPR-mediated Genome Editing Restores Dystrophin Expression and Function in mdx Mice
Xu, L., Park, K. H., Zhao, L., Xu, J., El Refaey, M., Gao, Y., Zhu, H., Ma, J., & Han, R. (2016) · Molecular Therapy · doi:10.1038/mt.2015.192 · Cited by 244 · see citing works
The rapidly evolving view of lysosomal storage diseases
Parenti, G., Medina, D. L., & Ballabio, A. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202012836 · Cited by 230 · see citing works
“Additionally, CRISPR/Cas9 can be by itself an alternative therapeutic option for treating LSDs by correcting disease-causing mutations, both in vitro and in vivo (Schwank et al, 2013; Wu et al, 2013; Xie et al, 2014).”
BackgroundCRISPR-Cpf1 correction of muscular dystrophy mutations in human cardiomyocytes and mice
Zhang, Y., Long, C., Li, H. Z., McAnally, J., Baskin, K. K., Shelton, J. M., Bassel‐Duby, R., & Olson, E. N. (2017) · Science Advances · doi:10.1126/sciadv.1602814 · Cited by 228 · see citing works
CRISPR-Cas9 delivery to hard-to-transfect cells via membrane deformation
Han, X., Liu, Z., Jo, M. C., Zhang, K., Li, Y., Zeng, Z., Li, N., Zu, Y., & Qin, L. (2015) · Science Advances · doi:10.1126/sciadv.1500454 · Cited by 232 · see citing works
A CRISPR view of developmentPreprint
Harrison, M. M., Jenkins, B., O’Connor-Giles, K. M., & Wildonger, J. (2014) · Genes & Development · doi:10.1101/gad.248252.114 · Cited by 228 · see citing works
“RGNs were used in mouse embryos to correct a dominant mutation in the Crygc gene, which causes cataracts, and those mice with the corrected locus were free of cataracts (Wu et al. 2013).”
MethodMacrophage-Specific in Vivo Gene Editing Using Cationic Lipid-Assisted Polymeric Nanoparticles
Luo, Y., Xu, C., Li, H., Cao, Z., Liu, J., Wang, J., Du, X., Yang, X., Gu, Z., & Wang, J. (2018) · ACS Nano · doi:10.1021/acsnano.7b07874 · Cited by 223 · see citing works
CRISPR-based rapid and ultra-sensitive diagnostic test for Mycobacterium tuberculosis
Ai, J., Zhou, X., Xu, T., Yang, M., Chen, Y., He, G., Pan, N., Cai, Y., Li, Y., Wang, X., et al. (2019) · Emerging Microbes & Infections · doi:10.1080/22221751.2019.1664939 · Cited by 220 · see citing works
“Cas9 was the first member of the Cas family which had been used for gene editing since 2013 [7,8].”
MethodA single-embryo, single-cell time-resolved model for mouse gastrulation
Mittnenzweig, M., Mayshar, Y., Cheng, S., Ben-Yair, R., Hadas, R., Rais, Y., Chomsky, E., Reines, N., Uzonyi, A., Lumerman, L., et al. (2021) · Cell · doi:10.1016/j.cell.2021.04.004 · Cited by 214 · see citing works
CRISPR‐Cas Biochemistry and CRISPR‐Based Molecular Diagnostics
Weng, Z., You, Z., Yang, J., Mohammad, N., Lin, M., Wei, Q., Gao, X., & Zhang, Y. (2023) · Angewandte Chemie International Edition · doi:10.1002/anie.202214987 · Cited by 211 · see citing works
CRISPR-Cas: New Tools for Genetic Manipulations from Bacterial Immunity Systems
Jiang, W., & Marraffini, L. A. (2015) · Annual Review of Microbiology · doi:10.1146/annurev-micro-091014-104441 · Cited by 210 · see citing works
CRISPR-Cas9–based treatment of myocilin-associated glaucoma
Jain, A., Zode, G. S., Kasetti, R. B., Ran, F. A., Yan, W. X., Sharma, T. P., Bugge, K., Searby, C. C., Fingert, J. H., Zhang, F., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1706193114 · Cited by 205 · see citing works
“Previously reported in vivo uses of CRISPR-Cas9 include correction of a dominant loss-of-function cataract-causing mutation in mouse embryos (39), HDR in a mouse model of type I tyrosinemina (40), correction of retinal dystrophy in a rat model of autosomal dominant retinitis pigmentosa (41), NHEJ-mediated gene disrupt…”
BackgroundCRISPR-Cas9: a new and promising player in gene therapy
Xiao-Jie, L., Hui-Ying, X., Zun-Ping, K., Jin-Lian, C., & Li-Juan, J. (2015) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2014-102968 · Cited by 200 · see citing works
Comparison of non-canonical PAMs for CRISPR/Cas9-mediated DNA cleavage in human cells
Zhang, Y., Ge, X., Yang, F., Zhang, L., Zheng, J., Tan, X., Jin, Z., Qu, J., & Gu, F. (2014) · Scientific Reports · doi:10.1038/srep05405 · Cited by 199 · see citing works
CRISPR-Cas Tools and Their Application in Genetic Engineering of Human Stem Cells and Organoids
Hendriks, D. F. G., Clevers, H. C., & Artegiani, B. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.10.014 · Cited by 196 · see citing works
A review of emerging physical transfection methods for CRISPR/Cas9-mediated gene editing
Fajrial, A. K., He, Q., Wirusanti, N. I., Slansky, J. E., & Ding, X. (2020) · Theranostics · doi:10.7150/thno.43465 · Cited by 198 · see citing works
“For example, a mutation on the Crygc gene caused cataract in mice [144].”
BackgroundCRISPR/Cas9-mediated targeted chromosome elimination
Zuo, E., Huo, X., Yao, X., Hu, X., Sun, Y., Yin, J., He, B., Wang, X., Shi, L., Ping, J., et al. (2017) · Genome biology · doi:10.1186/s13059-017-1354-4 · Cited by 188 · see citing works
Off-target predictions in CRISPR-Cas9 gene editing using deep learning
Lin, J., & Wong, K.-C. (2018) · Bioinformatics · doi:10.1093/bioinformatics/bty554 · Cited by 185 · see citing works
Development of CRISPR-Cas systems for genome editing and beyond
Zhang, F. (2019) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583519000052 · Cited by 185 · see citing works
“Before the year’s end, the first reports were published on the use of Cas9 to correct a cataractcausing mutation in a mouse, leading to reversal of the disease phenotype (Wu et al., 2013).”
BackgroundYoshimi, K., Kaneko, T., Voigt, B., & Mashimo, T. (2014) · Nature Communications · doi:10.1038/ncomms5240 · Cited by 177 · see citing works
“In mice, the high efficiency of HDR-mediated KIs has also been reported with ssODN donors 26,27,33 , compared with those of KIs with dsDNA donor vectors 39 .”
Guan, Y., Ma, Y., Li, Q., Sun, Z., Ma, L., Wu, L., Wang, L., Zeng, L., Shao, Y., Chen, Y., et al. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201506039 · Cited by 178 · see citing works
“…have shown potential applications of the CRISPR/Cas9 system for correction of genetic disorders in cells or mouse embryos (Schwank et al, 2013; Wu et al, 2013; Long et al, 2014), as well as prevention of cardiovascular disease in adult mice through disruption of the PCSK9 gene (Ding et al,…”
BackgroundRecent Progress in CRISPR/Cas9 Technology
Mei, Y., Wang, Y., Chen, H., Sun, Z. S., & Ju, X. (2016) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2016.01.001 · Cited by 181 · see citing works
“…Cas9 RNA/DSB Rosa26 7/7 Cytoplasm Cas9 RNA/DSB Fujita and Fujii, 2013 Hprt 17/18 Cytoplasm Cas9 RNA/DSB Crygc 13/23 Cytoplasm Cas9 px330/DSB Wu et al., 2013 Cetn1 10/17 Pronucleus Cas9 px330/DSB Mashiko et al., 2014 Cetn1 5/20 Cytoplasm Cas9 RNA/DSB Prm1 2/3 Pronucleus Cas9 px330/DSB Prm1…”
Efficient and Allele-Specific Genome Editing of Disease Loci in Human iPSCs
Smith, C. J., Abalde-Atristain, L., He, C., Brodsky, B. R., Braunstein, E. M., Chaudhari, P., Jang, Y.-Y., Cheng, L., & Ye, Z. (2014) · Molecular Therapy · doi:10.1038/mt.2014.226 · Cited by 173 · see citing works
Advances in CRISPR-Cas9 genome engineering: lessons learned from RNA interference
Barrangou, R., Birmingham, A., Wiemann, S., Beijersbergen, R. L., Hornung, V., & Smith, A. V. B. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv226 · Cited by 164 · see citing works
“Cataracts Rescue of a dominant mutation in the Crygc gene that causes cataracts (108).”
BackgroundGenome Editing in Induced Pluripotent Stem Cells using CRISPR/Cas9
Jehuda, R. B., Shemer, Y., & Binah, O. (2018) · Stem Cell Reviews and Reports · doi:10.1007/s12015-018-9811-3 · Cited by 162 · see citing works
Lipid nanoparticles for short interfering RNA delivery
Leung, A. K. K., Tam, Y. Y. C., & Cullis, P. R. (2014) · Advances in genetics · doi:10.1016/b978-0-12-800148-6.00004-3 · Cited by 158 · see citing works
“Cataract-free mice have been generated by injecting Cas9 mRNA and gRNA targeting the mutated Crygc gene locus into mouse zygotes followed by implantation in surrogate female mice (Wu et al., 2013).”
Generation of Genomic Deletions in Mammalian Cell Lines via CRISPR/Cas9
Bauer, D. E., Canver, M. C., & Orkin, S. H. (2014) · Journal of Visualized Experiments · doi:10.3791/52118 · Cited by 158 · see citing works
A general strategy to construct small molecule biosensors in eukaryotes
Feng, J., Jester, B. W., Tinberg, C. E., Mandell, D. J., Antunes, M. S., Chari, R., Morey, K. J., Rios, X., Medford, J. I., Church, G. M., et al. (2015) · eLife · doi:10.7554/elife.10606 · Cited by 158 · see citing works
“This switch-like control over CRISPR/Cas9 activity could reduce background activity and off-target editing, a critical feature for safer gene therapies (Mandal, et al., 2014; Wu et al., 2013; Schwank et al., 2013).”
Oligonucleotide‐directed mutagenesis for precision gene editing
Sauer, N. J., Mozoruk, J., Miller, R. B., Warburg, Z. J., Walker, K. A. M., Beetham, P. R., Schöpke, C. R., & Gocal, G. F. W. (2015) · Plant Biotechnology Journal · doi:10.1111/pbi.12496 · Cited by 155 · see citing works
“…editing in combination with oligonucleotides, primarily in eukaryotic systems (Chen et al., 2011; Connelly et al., 2010; DiCarlo et al., 2013; Gratz et al., 2013; Strouse et al., 2014; Suzuki et al., 2003; Svitashev et al., 2015; Voytas, 2013; Wang et al., 2015; Wu et al., 2013; Zhao et al., 2014).”
BackgroundGenome editing using CRISPR/Cas9-based knock-in approaches in zebrafish
Albadri, S., Bene, F. D., & Revenu, C. (2017) · Methods · doi:10.1016/j.ymeth.2017.03.005 · Cited by 152 · see citing works
Araki, M., & Ishii, T. (2014) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-12-108 · Cited by 150 · see citing works
“Genome editing technology is more likely to develop into medicine for preventing a genetic disease if corrective genome editing is integrated into assisted reproductive technology (ART), including IVF and ICSI.”
BackgroundInfluentialGraphene oxide-mediated Cas9/sgRNA delivery for efficient genome editing
Yue, H., Zhou, X., Cheng, M., & Xing, D. (2018) · Nanoscale · doi:10.1039/c7nr07999k · Cited by 150 · see citing works
CRISPR/Cas9 technology as a potent molecular tool for gene therapy
Karimian, A., Azizian, K., Parsian, H., Rafieyan, S., Shafiei‐Irannejad, V., Kheyrollah, M., Yousefi, M., Majidinia, M., & Yousefi, B. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.27972 · Cited by 144 · see citing works
Complementary Alu sequences mediate enhancer–promoter selectivity
Liang, L., Cao, C., Ji, L., Cai, Z., Wang, D., Ye, R., Chen, J., Yu, X., Zhou, J., Bai, Z., et al. (2023) · Nature · doi:10.1038/s41586-023-06323-x · Cited by 138 · see citing works
Nanoparticles for nucleic acid delivery: Applications in cancer immunotherapy
Mukalel, A. J., Riley, R., Zhang, R., & Mitchell, M. J. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.04.040 · Cited by 140 · see citing works
CRISPR-Based Diagnosis of Infectious and Noninfectious Diseases
vangah, S. J., Katalani, C., Boone, H. A., Hajizade, A., Sijerčić, A., & Ahmadian, G. (2020) · Biological Procedures Online · doi:10.1186/s12575-020-00135-3 · Cited by 137 · see citing works
“cluding mice [86], Drosophila [8], Caenorhabditis elegans [21], humans [15, 17, 39, 69], zebrafish [32],”
BackgroundDelivery and therapeutic applications of gene editing technologies ZFNs, TALENs, and CRISPR/Cas9
LaFountaine, J. S., Fathe, K., & Smyth, H. D. C. (2015) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2015.08.029 · Cited by 137 · see citing works
Weninger, A., Fischer, J. E., Raschmanová, H., Kniely, C., Vogl, T., & Glieder, A. (2017) · Journal of Cellular Biochemistry · doi:10.1002/jcb.26474 · Cited by 129 · see citing works
Responsive Nanocarriers as an Emerging Platform for Cascaded Delivery of Nucleic Acids to Cancer
Liu, Y., Xu, C., Iqbal, S., Yang, X., & Wang, J. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.03.004 · Cited by 130 · see citing works
“tivemutations and the disruption of viral DNA inmany diseases, such as tumor [48], cataracts [49], cystic fibrosis [50], hereditary tyrosinemia [51,52], human immunodeficiency virus [53] et al.”
Loureiro, A., & Silva, G. (2019) · Antibiotics · doi:10.3390/antibiotics8010018 · Cited by 129 · see citing works
“Due to the low rate of HDR recombination [109], and because it is only readily available in dividing cells [110,111], this method needs to become more robust and flexible in order to see use in disease therapy.”
CRISPR/Cas9‐mediated genome editing: From basic research to translational medicine
Jacinto, F. V., Link, W., & Ferreira, B. I. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14916 · Cited by 130 · see citing works
Zhong, C., Yin, Q., Xie, Z., Bai, M., Dong, R., Tang, W., Xing, Y., Zhang, H., Yang, S., Chen, L., et al. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.06.005 · Cited by 119 · see citing works
“To test this, we used CRISPRCas9 technology (Wu et al., 2013).”
MethodCourtney, D., Moore, J. E., Atkinson, S. D., Maurizi, E., Allen, E. H. A., Pedrioli, D. M. L., McLean, W. H. I., Nesbit, M. A., & Moore, T. (2015) · Gene Therapy · doi:10.1038/gt.2015.82 · Cited by 124 · see citing works
Genome editing with CRISPR/Cas9 in postnatal mice corrects PRKAG2 cardiac syndrome
Xie, C., Zhang, Y., Song, L., Luo, J., Qi, W., Hu, J., Lu, D., Yang, Z. H., Zhang, J., Xiao, J., et al. (2016) · Cell Research · doi:10.1038/cr.2016.101 · Cited by 125 · see citing works
Protospacer adjacent motif (PAM)-distal sequences engage CRISPR Cas9 DNA target cleavage
Cencic, R., Miura, H., Malina, A., Robert, F., Ethier, S., Schmeing, T. M., Dostie, J., & Pelletier, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0109213 · Cited by 117 · see citing works
Temporal regulation of prenatal embryonic development by paternal imprinted loci
Li, Q., Li, Y., Yin, Q., Huang, S., Wang, K., Zhuo, L., Li, W., Chang, B., & Li, J. (2019) · Science China Life Sciences · doi:10.1007/s11427-019-9817-6 · Cited by 120 · see citing works
Ma, M., Zhuang, F., Hu, X., Wang, B., Wen, X., Ji, J., & Xi, J. (2017) · Cell Research · doi:10.1038/cr.2017.29 · Cited by 116 · see citing works
CUT-PCR: CRISPR-mediated, ultrasensitive detection of target DNA using PCR
Lee, S. H., Yu, J., Hwang, G.-H., Kim, S., Kim, H. S., Ye, S., Kim, K., Park, J., Park, D. Y., Cho, Y.-K., et al. (2017) · Oncogene · doi:10.1038/onc.2017.281 · Cited by 111 · see citing works
Wan, T. Y., Niu, D., Wu, C., Xu, F., Church, G. M., & Yuan, P. (2019) · Materials Today · doi:10.1016/j.mattod.2018.12.003 · Cited by 118 · see citing works
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 118 · see citing works
Slijkerman, R. W. N., Song, F., Astuti, G., Huynen, M. A., van Wijk, E., Stieger, K., & Collin, R. W. J. (2015) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2015.04.004 · Cited by 114 · see citing works
“First tests in a mouse model for cataracts showed successful repair of the mutated Crygc gene by using its healthy counterpart as a template, which led to fertile wildtype mice (Wu et al., 2013).”
BackgroundCRISPR/Cas9 Genome-Editing System in Human Stem Cells: Current Status and Future Prospects
Zhang, Z., Zhang, Y., Gao, F., Han, S., Cheah, K. S. E., Tse, H., & Lian, Q. (2017) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2017.09.009 · Cited by 116 · see citing works
Genome Editing of eIF4E1 in Tomato Confers Resistance to Pepper Mottle Virus
Yoon, Y.-J., Venkatesh, J., Lee, J., Kim, J., Lee, H., Kim, D.-S., & Kang, B. (2020) · Frontiers in Plant Science · doi:10.3389/fpls.2020.01098 · Cited by 114 · see citing works
“CRISPR/Cas9 has been utilized for site-directed mutagenesis in microbes, animals, human cells, and plants (Jiang et al., 2013; Wu et al., 2013; Zhang et al., 2017; Shapiro et al., 2018).”
Method
- Authors
- Wu, Y., Liang, D., Wang, Y., Bai, M., Tang, W., Bao, S., Yan, Z., Li, D., & Li, J.
- Affiliations
- Chinese Academy of Sciences (CN)
- Corresponding author
- Li, Jinsong
- Venue
- Cell stem cell
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 13
- Issue
- 6
- Pages
- 659-662
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2058792860
- Cited by
- 614
- References
- 20
- Citations by year
- 2026: 14 · 2025: 19 · 2024: 26 · 2023: 34 · 2022: 34 · 2021: 51 · 2020: 51 · 2019: 61 · 2018: 67 · 2017: 64 · 2016: 69 · 2015: 68 · 2014: 54 · 2013: 2
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- CRISPR/Cas9, gene correction, cataract, dominant mutations, homology-directed repair, single guide RNA, zygote injection, off-target effects, germline transmission, mouse model
- MeSH terms
- Animals, Base Sequence, Cataract, Disease Models, Animal, Molecular Sequence Data, RNA, Messenger, Genetic Therapy, gamma-Crystallins, Mice, Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR-Associated Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
