Generation of mouse models of myeloid malignancy with combinatorial genetic lesions using CRISPR-Cas9 genome editing
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Genome sequencing studies have shown that human malignancies often bear mutations in four or more driver genes, but it is difficult to recapitulate this degree of genetic complexity in mouse models using conventional breeding. Here we use the CRISPR-Cas9 system of genome editing to overcome this limitation. By delivering combinations of small guide RNAs (sgRNAs) and Cas9 with a lentiviral vector, we modified up to five genes in a single mouse hematopoietic stem cell (HSC), leading to clonal outgrowth and myeloid malignancy. We thereby generated models of acute myeloid leukemia (AML) with cooperating mutations in genes encoding epigenetic modifiers, transcription factors and mediators of cytokine signaling, recapitulating the combinations of mutations observed in patients. Our results suggest that lentivirus-delivered sgRNA:Cas9 genome editing should be useful to engineer a broad array of in vivo cancer models that better reflect the complexity of human disease.
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Viral vectors have been extensively applied to deliver CRISPR cassettes in vitro and in vivo largely owing to their high efficiency in gene delivery and long-term stable transgene expression.
“In recent years, viral vectors have been extensively applied to deliver CRISPR cassettes in vitro and in vivo largely owing to their high efficiency in gene delivery and long-term stable transgene expression [34, 58, 65].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [34]
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Cites
A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity
Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., & Charpentier, E. (2012) · Science · doi:10.1126/science.1225829 · Cited by 17,116 · see citing works
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
Genome-scale CRISPR-Cas9 knockout screening in human cells
Shalem, O., Sanjana, N. E., Hartenian, E., Shi, X., Scott, D. A., Mikkelsen, T. S., Heckl, D., Ebert, B. L., Root, D. E., Doench, J. G., et al. (2014) · Science · doi:10.1126/science.1247005 · Cited by 5,234 · see citing works
Self-citationGenomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia
The Cancer Genome Atlas Research Network (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1301689 · Cited by 5,078 · 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
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
Genetic screens in human cells using the CRISPR-Cas9 system
Wang, T., Wei, J. J., Sabatini, D. M., & Lander, E. S. (2014) · Science · doi:10.1126/science.1246981 · Cited by 2,856 · see citing works
Targeted genome modification of crop plants using a CRISPR-Cas system
Shan, Q., Wang, Y., Li, J., Zhang, Y., Chen, K., Liang, Z., Zhang, K., Liu, J., Xi, J., Qiu, J., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2650 · Cited by 1,965 · see citing works
Kim, J. H., Lee, S. R., Li, L.-H., Park, H., Park, J.-H., Lee, K. Y., Kim, M., Shin, B. A., & Choi, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018556 · Cited by 1,340 · see citing works
Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation
Moran-Crusio, K., Reavie, L., Shih, A., Abdel-Wahab, O., Ndiaye-Lobry, D., Lobry, C., Figueroa, M. E., Vasanthakumar, A., Patel, J., Zhao, X., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.06.001 · Cited by 1,339 · see citing works
FLASH assembly of TALENs for high-throughput genome editing
Reyon, D., Tsai, S. Q., Khayter, C., Foden, J. A., Sander, J. D., & Joung, J. K. (2012) · Nature Biotechnology · doi:10.1038/nbt.2170 · Cited by 1,171 · see citing works
Dnmt3a is essential for hematopoietic stem cell differentiation
Challen, G. A., Sun, D., Jeong, M., Luo, M., Jelinek, J., Berg, J. S., Bock, C., Vasanthakumar, A., Gu, H., Xi, Y., et al. (2012) · Nature Genetics · doi:10.1038/ng.1009 · Cited by 1,122 · see citing works
Quivoron, C., Couronné, L., Della Valle, V., Lopez, C. K., Plo, I., Wagner-Ballon, O., Do Cruzeiro, M., Delhommeau, F., Arnulf, B., Stern, M.-H., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.06.003 · Cited by 924 · 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
Targeted Genome Editing Across Species Using ZFNs and TALENs
Wood, A. J., Lo, T., Zeitler, B., Pickle, C. S., Ralston, E. J., Lee, A. H., Amora, R., Miller, J. C., Leung, E., Meng, X., et al. (2011) · Science · doi:10.1126/science.1207773 · Cited by 664 · see citing works
Murine Leukemia Induced by Retroviral Gene Marking
Li, Z., Düllmann, J., Schiedlmeier, B., Schmidt, M., Kalle, C. V., Meyer, J., Forster, M., Stocking, C., Wahlers, A., Frank, O., et al. (2002) · Science · doi:10.1126/science.1068893 · Cited by 653 · see citing works
Targeted gene disruption in somatic zebrafish cells using engineered TALENs
Sander, J. D., Cade, L., Khayter, C., Reyon, D., Peterson, R. T., Joung, J. K., & Yeh, J.-R. J. (2011) · Nature Biotechnology · doi:10.1038/nbt.1934 · Cited by 622 · see citing works
G ENETICS OF M YELOID L EUKEMIAS
Kelly, L. M., & Gilliland, D. G. (2002) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.3.032802.115046 · Cited by 522 · see citing works
An Oncogenomics-Based In Vivo RNAi Screen Identifies Tumor Suppressors in Liver Cancer
Zender, L., Xue, W., Zuber, J. A., Semighini, C. P., Krasnitz, A., Ma, B., Zender, P., Kubicka, S., Luk, J. M., Schirmacher, P., et al. (2008) · Cell · doi:10.1016/j.cell.2008.09.061 · Cited by 425 · see citing works
Physiological Promoters Reduce the Genotoxic Risk of Integrating Gene Vectors
Zychlinski, D., Schambach, A., Modlich, U., Maetzig, T., Meyer, J., Grassman, E., Mishra, A., & Baum, C. (2008) · Molecular Therapy · doi:10.1038/mt.2008.5 · Cited by 271 · see citing works
Lee, B. H., Tóthová, Z., Levine, R. L., Anderson, K., Buza-Vidas, N., Cullen, D. E., McDowell, E. P., Adelsperger, J., Fröhling, S., Huntly, B. J. P., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.08.031 · Cited by 228 · see citing works
Ezh2 augments leukemogenicity by reinforcing differentiation blockage in acute myeloid leukemia.
Tanaka, S., Miyagi, S., Sashida, G., Chiba, T., Yuan, J., Mochizuki-Kashio, M., Suzuki, Y., Sugano, S., Nakaseko, C., Yokote, K., et al. (2012) · Blood · doi:10.1182/blood-2011-11-394932 · Cited by 201 · see citing works
Schambach, A., Bohne, J., Chandra, S., Will, E., Margison, G. P., Williams, D. A., & Baum, C. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.08.012 · Cited by 197 · see citing works
Morozova, K. S., Piatkevich, K. D., Gould, T. J., Zhang, J., Bewersdorf, J., & Verkhusha, V. V. (2010) · Biophysical Journal · doi:10.1016/j.bpj.2010.04.025 · Cited by 159 · see citing works
A tumour suppressor network relying on the polyamine–hypusine axis
Scuoppo, C., Miething, C., Lindqvist, L., Reyes, J., Ruse, C. I., Appelmann, I., Yoon, S. C., Krasnitz, A., Teruya‐Feldstein, J., Pappin, D., et al. (2012) · Nature · doi:10.1038/nature11126 · Cited by 141 · see citing works
Quantitative effects of Nf1 inactivation on in vivo hematopoiesis
Zhang, Y., Taylor, B. R., Shannon, K., & Clapp, D. W. (2001) · Journal of Clinical Investigation · doi:10.1172/jci12758 · Cited by 54 · see citing works
Mead, A. J., Kharazi, S., Atkinson, D., Macaulay, I. C., Pecquet, C., Loughran, S. J., Lutteropp, M., Woll, P. S., Chowdhury, O., Luc, S., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.04.031 · Cited by 44 · see citing works
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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
Li, H., Yang, Y., Hong, W., Huang, M., Wu, M., & Zhao, X. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0089-y · Cited by 1,771 · 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
Modeling colorectal cancer using CRISPR-Cas9–mediated engineering of human intestinal organoids
Matano, M., Date, S., Shimokawa, M., Takano, A., Fujii, M., Ohta, Y., Watanabe, T., Kanai, T., & Sato, T. (2015) · Nature Medicine · doi:10.1038/nm.3802 · Cited by 1,135 · see citing works
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
Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS
Krönke, J., Fink, E. C., Hollenbach, P. W., MacBeth, K. J., Hurst, S. N., Udeshi, N. D., Chamberlain, P. P., Mani, D. R., Man, H. W., Gandhi, A. K., et al. (2015) · Nature · doi:10.1038/nature14610 · Cited by 863 · see citing works
Self-citationNon-coding recurrent mutations in chronic lymphocytic leukaemia
Puente, X. S., Beà, S., Valdés‐Mas, R., Villamor, N., Gutiérrez‐Abril, J., Martín-Subero, J. I., Munar, M., Rubio-Pérez, C., Jares, P., Aymerich, M., et al. (2015) · Nature · doi:10.1038/nature14666 · Cited by 813 · see citing works
Delivery strategies of the CRISPR-Cas9 gene-editing system for therapeutic applications
Liu, C., Zhang, L., Liu, H., & Cheng, K. (2017) · Journal of Controlled Release · doi:10.1016/j.jconrel.2017.09.012 · Cited by 607 · 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
Am I ready for CRISPR? A user's guide to genetic screens
Doench, J. G. (2018) · Nature Reviews Genetics · doi:10.1038/nrg.2017.97 · Cited by 452 · see citing works
CRISPR in cancer biology and therapy
Katti, A., Diaz, B. J., Caragine, C. M., Sanjana, N. E., & Dow, L. E. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00441-w · Cited by 440 · see citing works
Sano, S., Oshima, K., Wang, Y., Katanasaka, Y., Sano, M., & Walsh, K. (2018) · Circulation Research · doi:10.1161/circresaha.118.313225 · Cited by 417 · see citing works
Non-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
Applications of the CRISPR-Cas9 system in cancer biology
Sánchez-Rivera, F. J., & Jacks, T. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3950 · Cited by 405 · see citing works
Multiplex CRISPR/Cas9-based genome engineering from a single lentiviral vector
Kabadi, A. M., Ousterout, D. G., Hilton, I. B., & Gersbach, C. A. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku749 · Cited by 371 · see citing works
Mitochondrial Reprogramming Underlies Resistance to BCL-2 Inhibition in Lymphoid Malignancies
Guièze, R., Liu, V. M., Rosebrock, D., Jourdain, A. A., Hernández-Sánchez, M., Martinez Zurita, A., Sun, J., Ten Hacken, E., Baranowski, K., Thompson, P. A., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.08.005 · Cited by 361 · see citing works
The Dynamic Landscape of Open Chromatin during Human Cortical Neurogenesis
de la Torre-Ubieta, L., Stein, J. L., Won, H., Opland, C. K., Liang, D., Lu, D., & Geschwind, D. H. (2018) · Cell · doi:10.1016/j.cell.2017.12.014 · Cited by 353 · see citing works
In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis
Roper, J., Tammela, T., Cetinbas, N. M., Akkad, A., Roghanian, A., Rickelt, S., Almeqdadi, M., Wu, K., Oberli, M. A., Rivera, F. J. S., et al. (2017) · Nature Biotechnology · doi:10.1038/nbt.3836 · Cited by 345 · see citing works
Lipid accumulation induced by APOE4 impairs microglial surveillance of neuronal-network activity
Victor, M. B., Leary, N., Luna, X., Meharena, H. S., Scannail, A. N., Bozzelli, P. L., Samaan, G., Murdock, M. H., von Maydell, D., Effenberger, A. H., et al. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2022.07.005 · Cited by 316 · see citing works
Refined sgRNA efficacy prediction improves large- and small-scale CRISPR–Cas9 applications
Labuhn, M., Adams, F. F., Ng, M. S. W., Knoess, S., Schambach, A., Charpentier, E., Schwarzer, A., Mateo, J. L., Klusmann, J., & Heckl, D. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1268 · Cited by 289 · see citing works
Self-citationCRISPR-Cas9: A Preclinical and Clinical Perspective for the Treatment of Human Diseases
Sharma, G., Sharma, A. R., Bhattacharya, M., Lee, S., & Chakraborty, C. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.09.028 · Cited by 295 · see citing works
Resident and Monocyte-Derived Macrophages in Cardiovascular Disease
Honold, L., & Nahrendorf, M. (2018) · Circulation Research · doi:10.1161/circresaha.117.311071 · Cited by 272 · see citing works
Core circadian clock genes regulate leukemia stem cells in AML
Puram, R. V., Kowalczyk, M. S., de Boer, C. G., Schneider, R. K., Miller, P. G., McConkey, M., Tothova, Z., Tejero, H., Heckl, D., Järås, M., et al. (2016) · Cell · doi:10.1016/j.cell.2016.03.015 · Cited by 274 · see citing works
Self-citationViral Delivery Systems for CRISPR
Xu, C. L., Ruan, M. Z. C., Mahajan, V. B., & Tsang, S. H. (2019) · Viruses · doi:10.3390/v11010028 · Cited by 277 · see citing works
Highly Efficient Genome Editing of Murine and Human Hematopoietic Progenitor Cells by CRISPR/Cas9
Gundry, M. C., Brunetti, L., Lin, A., Mayle, A. E., Kitano, A., Wagner, D., Hsu, J. I., Hoegenauer, K. A., Rooney, C. M., Goodell, M. A., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.09.092 · Cited by 265 · see citing works
“Several delivery methods have been used to perform CRISPR/Cas9mediated gene editing of HSPCs, including lentiviral transduction (Heckl et al., 2014), plasmid DNA transfection (Mandal et al.”
MethodGenomic deletion of malic enzyme 2 confers collateral lethality in pancreatic cancer
Dey, P., Baddour, J., Muller, F., Wu, C. C., Wang, H., Liao, W.-T., Lan, Z., Chen, A., Gutschner, T., Kang, Y., et al. (2017) · Nature · doi:10.1038/nature21052 · Cited by 264 · see citing works
Sublethal cytochrome c release generates drug-tolerant persister cells
Kalkavan, H., Chen, J., Crawford, J. C., Quarato, G., FITZGERALD, P. J., Tait, S. W. G., Goding, C. R., & Green, D. R. (2022) · Cell · doi:10.1016/j.cell.2022.07.025 · Cited by 267 · see citing works
Interferon-γ induces tumor resistance to anti-PD-1 immunotherapy by promoting YAP phase separation
Yu, M., Peng, Z., Qin, M., Liu, Y., Wang, J., Zhang, C., Lin, J., Dong, T., Wang, L., Li, S., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.01.010 · Cited by 250 · 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
Kahn, J. D., Miller, P. G., Silver, A. J., Sellar, R. S., Bhatt, S., Gibson, C., McConkey, M., Adams, D., Mar, B., Mertins, P., et al. (2018) · Blood · doi:10.1182/blood-2018-05-850339 · Cited by 225 · see citing works
Self-citationTargeted DNA methylation in vivo using an engineered dCas9-MQ1 fusion protein
Lei, Y., Zhang, X., Su, J., Jeong, M., Gundry, M. C., Huang, Y.-H., Zhou, Y., Li, W., & Goodell, M. A. (2017) · Nature Communications · doi:10.1038/ncomms16026 · Cited by 218 · see citing works
Transgenic Mouse Models in Cancer Research
Tratar, U. L., Horvat, S., & Čemažar, M. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00268 · Cited by 216 · see citing works
Herranz, D., Ambesi‐Impiombato, A., Sudderth, J., Sánchez-Martín, M., Belver, L., Tosello, V., Xu, L., Wendorff, A. A., Castillo-Martín, M., Haydu, J. E., et al. (2015) · Nature Medicine · doi:10.1038/nm.3955 · Cited by 210 · see citing works
Engineered materials for in vivo delivery of genome-editing machinery
Tong, S., Moyo, B., Lee, C. M., Leong, K. W., & Bao, G. (2019) · Nature Reviews Materials · doi:10.1038/s41578-019-0145-9 · Cited by 206 · see citing works
Challenges in CRISPR/CAS9 delivery: potential roles of nonviral vectors
Li, L., He, Z.-Y., Wei, X.-W., Gao, G.-P., & Wei, Y.-Q. (2015) · Human Gene Therapy · doi:10.1089/hum.2015.069 · Cited by 202 · see citing works
PLA2G6 guards placental trophoblasts against ferroptotic injury
Beharier, O., Tyurin, V. A., Goff, J. P., Guerrero-Santoro, J., Kajiwara, K., Chu, T., Tyurina, Y. Y., St Croix, C. M., Wallace, C. T., Parry, S., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2009201117 · Cited by 198 · see citing works
Delivery and Specificity of CRISPR/Cas9 Genome Editing Technologies for Human Gene Therapy
Gori, J. L., Hsu, P. D., Maeder, M. L., Shen, S., Welstead, G. G., & Bumcrot, D. A. (2015) · Human Gene Therapy · doi:10.1089/hum.2015.074 · Cited by 192 · see citing works
HOTTIP lncRNA Promotes Hematopoietic Stem Cell Self-Renewal Leading to AML-like Disease in Mice
Luo, H., Zhu, G., Xu, J., Lai, Q., Yan, B., Guo, Y., Fung, T. K., Zeisig, B. B., Cui, Y., Zha, J., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.10.011 · Cited by 192 · see citing works
CRISPR–Cas: a tool for cancer research and therapeutics
Yin, H., Xue, W., & Anderson, D. G. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0166-8 · Cited by 178 · see citing works
Maresch, R., Mueller, S., Veltkamp, C., Öllinger, R., Friedrich, M., Heid, I., Steiger, K., Weber, J., Engleitner, T., Barenboim, M., et al. (2016) · Nature Communications · doi:10.1038/ncomms10770 · Cited by 166 · see citing works
mTOR signaling in tumorigenesis
Xu, K. L., Liu, P., & Wei, W. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.10.007 · Cited by 167 · 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
Patterns of CRISPR/Cas9 activity in plants, animals and microbes
Bortesi, L., Zhu, C., Zischewski, J., Pérez, L., Bassié, L., Nadi, R., Forni, G., Lade, S. B., Soto, E., Jin, X., et al. (2016) · Plant Biotechnology Journal · doi:10.1111/pbi.12634 · Cited by 159 · see citing works
CRISPR-Cas for genome editing: Classification, mechanism, designing and applications
Bhatia, S. K., ., P., & Yadav, S. K. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.124054 · Cited by 165 · see citing works
The SS18-SSX Oncoprotein Hijacks KDM2B-PRC1.1 to Drive Synovial Sarcoma
Banito, A., Li, X., Laporte, A. N., Roe, J., Sánchez-Vega, F., Huang, C., Dancsok, A. R., Hatzi, K., Chen, C.-C., Tschaharganeh, D. F., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.01.018 · Cited by 158 · see citing works
Meyer, S. N., Scuoppo, C., Vlasevska, S., Bal, É., Holmes, A. B., Holloman, M., Garcia‐Ibanez, L., Nataraj, S. E., Duval, R., Vantrimpont, T., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.08.006 · Cited by 153 · see citing works
Histone editing elucidates the functional roles of H3K27 methylation and acetylation in mammals
Sankar, A., Mohammad, F., Sundaramurthy, A. K., Wang, H., Lerdrup, M., Tatar, T., & Helin, K. (2022) · Nature Genetics · doi:10.1038/s41588-022-01091-2 · Cited by 152 · see citing works
CRISPR/Cas: Advances, Limitations, and Applications for Precision Cancer Research
Yang, Y., Xu, J., Ge, S., & Lai, L. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.649896 · Cited by 160 · see citing works
Dong, W., & Kantor, B. (2021) · Viruses · doi:10.3390/v13071288 · Cited by 153 · see citing works
Lenalidomide promotes the development of TP53 -mutated therapy-related myeloid neoplasms
Sperling, A. S., Guerra, V. A., Kennedy, J. A., Yan, Y., Hsu, J. I., Wang, F., Nguyen, A. T., Miller, P. G., McConkey, M. E., Barrios, V. A. Q., et al. (2022) · Blood · doi:10.1182/blood.2021014956 · Cited by 153 · see citing works
Self-citationLi, L., Yáng, Z., Zhu, S., He, L., Fan, W., Tang, W., Zou, J., Shen, Z., Zhang, M., Tang, L., et al. (2019) · Advanced Materials · doi:10.1002/adma.201901187 · Cited by 146 · see citing works
HOTTIP-dependent R-loop formation regulates CTCF boundary activity and TAD integrity in leukemia
Luo, H., Zhu, G., Eshelman, M. A., Fung, T. K., Lai, Q., Wang, F., Zeisig, B. B., Lesperance, J., Ma, X., Shi, C., et al. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.01.014 · Cited by 145 · see citing works
Recent advances and applications of CRISPR-Cas9 in cancer immunotherapy
Liu, Z., Shi, M., Ren, Y., Xu, H., Weng, S., Ning, W., Ge, X., Liu, L., Guo, C., Duo, M., et al. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01738-6 · Cited by 146 · see citing works
SETD2 alterations impair DNA damage recognition and lead to resistance to chemotherapy in leukemia
Mar, B. G., Chu, S. H., Kahn, J. D., Krivtsov, A. V., Koche, R. P., Castellano, C. A., Kotlier, J. L., Zon, R. L., McConkey, M. E., Chabon, J. R., et al. (2017) · Blood · doi:10.1182/blood-2017-03-775569 · Cited by 139 · see citing works
Self-citation3D Genome of macaque fetal brain reveals evolutionary innovations during primate corticogenesis
Luo, X., Liu, Y., Dang, D., Hu, T., Hou, Y., Meng, X., Zhang, F., Li, T., Wang, C., Li, M., et al. (2021) · Cell · doi:10.1016/j.cell.2021.01.001 · Cited by 137 · see citing works
Small molecule promotes β-catenin citrullination and inhibits Wnt signaling in cancer
Qu, Y., Olsen, J. R., Xing, Y., Cheng, P. F., Levesque, M. P., Brokstad, K. A., Hoffman, P. S., Oyan, A. M., Zhang, W., Kalland, K., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2510 · Cited by 141 · 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
Efficient delivery of nuclease proteins for genome editing in human stem cells and primary cells
Liu, J., Gaj, T., Yang, Y., Wang, N., Shui, S., Kim, S., Kanchiswamy, C. N., Kim, J., & Barbas, C. F. (2015) · Nature Protocols · doi:10.1038/nprot.2015.117 · Cited by 127 · see citing works
CRISPR/Cas9 gene-editing: Research technologies, clinical applications and ethical considerations
Memi, F., Ntokou, A., & Papangeli, I. (2018) · Seminars in Perinatology · doi:10.1053/j.semperi.2018.09.003 · Cited by 130 · see citing works
Bak, R. O., Dever, D. P., Reinisch, A., Cruz Hernandez, D., Majeti, R., & Porteus, M. H. (2017) · eLife · doi:10.7554/elife.27873 · Cited by 122 · see citing works
Tu, K., Deng, H., Kong, L., Wang, Y., Yang, T., Hu, Q., Hu, M. Y., Yang, C., & Zhang, Z. (2020) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.9b23084 · Cited by 122 · see citing works
A Non-catalytic Function of SETD1A Regulates Cyclin K and the DNA Damage Response
Hoshii, T., Cifani, P., Feng, Z., Huang, C., Koche, R. P., Chen, C.-W. D., Delaney, C. D., Lowe, S. W., Kentsis, A., & Armstrong, S. A. (2018) · Cell · doi:10.1016/j.cell.2018.01.032 · Cited by 120 · see citing works
A CRISPR-Cas9 delivery system for in vivo screening of genes in the immune system
LaFleur, M. W., Nguyen, T. H., Coxe, M. A., Yates, K. B., Trombley, J. D., Weiss, S. A., Brown, F. D., Gillis, J. E., Coxe, D. J., Doench, J. G., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09656-2 · Cited by 117 · see citing works
Cao, X., Chen, J., Li, B., Dang, J., Zhang, W., Zhong, X., Wang, C., Raoof, M., Sun, Z., Yu, J., et al. (2022) · Science Advances · doi:10.1126/sciadv.abl9171 · Cited by 117 · see citing works
Advances and perspectives on the use of CRISPR/Cas9 systems in plant genomics research
Liu, D., Hu, R., Palla, K. J., Tuskan, G. A., & Yang, X. (2016) · Current Opinion in Plant Biology · doi:10.1016/j.pbi.2016.01.007 · Cited by 115 · see citing works
A somatic role for the histone methyltransferase Setdb1 in endogenous retrovirus silencing
Kato, M., Takemoto, K., & Shinkai, Y. (2018) · Nature Communications · doi:10.1038/s41467-018-04132-9 · Cited by 94 · see citing works
Precision cancer mouse models through genome editing with CRISPR-Cas9
Mou, H., Kennedy, Z., Anderson, D. G., Yin, H., & Xue, W. (2015) · Genome Medicine · doi:10.1186/s13073-015-0178-7 · Cited by 113 · see citing works
Kerins, M. J., Milligan, J., Wohlschlegel, J. A., & Ooi, A. (2018) · Cancer Science · doi:10.1111/cas.13701 · Cited by 110 · see citing works
The Ftx Noncoding Locus Controls X Chromosome Inactivation Independently of Its RNA Products
Furlan, G., Hernandez, N. G., Huret, C., Galupa, R., van Bemmel, J. G., Romito, A., Heard, É., Morey, C., & Rougeulle, C. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.03.024 · Cited by 106 · see citing works
A glance at genome editing with CRISPR–Cas9 technology
Barman, A., Deb, B., & Chakraborty, S. (2019) · Current Genetics · doi:10.1007/s00294-019-01040-3 · Cited by 105 · see citing works
The SPPL3-Defined Glycosphingolipid Repertoire Orchestrates HLA Class I-Mediated Immune Responses
Jongsma, M. L. M., de Waard, A. A., Raaben, M., Zhang, T., Cabukusta, B., Platzer, R., Blomen, V. A., Xagara, A., Verkerk, T., Bliss, S., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.11.003 · Cited by 108 · see citing works
Clonal hematopoiesis, somatic mosaicism, and age-associated disease
Evans, M. A., & Walsh, K. (2022) · Physiological Reviews · doi:10.1152/physrev.00004.2022 · Cited by 105 · see citing works
Modeling Disease In Vivo With CRISPR/Cas9
Dow, L. E. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2015.07.006 · Cited by 105 · see citing works
Wang, G., Chow, R. D.-W., Ye, L., Guzman, C. D., Dai, X., Dong, M. B., Zhang, F., Sharp, P. A., Platt, R. J., & Chen, S. (2018) · Science Advances · doi:10.1126/sciadv.aao5508 · Cited by 100 · see citing works
Resources for the design of CRISPR gene editing experiments
Graham, D. B., & Root, D. E. (2015) · Genome biology · doi:10.1186/s13059-015-0823-x · Cited by 102 · see citing works
CRISPR technologies for stem cell engineering and regenerative medicine
Hsu, M., Chang, Y., Truong, V. A., Lai, P., Nguyen, T. K. N., & Hu, Y. (2019) · Biotechnology Advances · doi:10.1016/j.biotechadv.2019.107447 · Cited by 105 · see citing works
Carrier strategies boost the application of CRISPR/Cas system in gene therapy
Xu, Z., Wang, Q., Zhong, H., Jiang, Y., Shi, X., Yuan, B., Yu, N., Zhang, S., Yuan, X., Guo, S., et al. (2022) · Exploration · doi:10.1002/exp.20210081 · Cited by 104 · see citing works
Overview of the Use of Murine Models in Leukemia and Lymphoma Research
Kohnken, R. A., Porcu, P., & Mishra, A. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00022 · Cited by 102 · see citing works
Tóthová, Z., Krill-Burger, J. M., Popova, K. D., Landers, C. C., Sievers, Q. L., Yudovich, D., Belizaire, R., Aster, J. C., Morgan, E. A., Tsherniak, A., et al. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.07.015 · Cited by 96 · see citing works
Self-citationJacquelin, S., Straube, J., Cooper, L., Vu, T., Song, A., Bywater, M., Baxter, E., Heidecker, M., Wackrow, B., Porter, A., et al. (2018) · Blood · doi:10.1182/blood-2018-04-846220 · Cited by 99 · see citing works
Self-citationCRISPR/Cas System and Factors Affecting Its Precision and Efficiency
Javaid, N., & Choi, S. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.761709 · Cited by 98 · see citing works
Genetic screens and functional genomics using CRISPR /Cas9 technology
Hartenian, E., & Doench, J. G. (2015) · FEBS Journal · doi:10.1111/febs.13248 · Cited by 97 · see citing works
CRISPR/Cas9 – An evolving biological tool kit for cancer biology and oncology
Tian, X., Gu, T., Patel, S., Bode, A. M., Lee, M., & Dong, Z. (2019) · npj Precision Oncology · doi:10.1038/s41698-019-0080-7 · Cited by 98 · see citing works
Vitamin B6 Addiction in Acute Myeloid Leukemia
Chen, C.-C., Li, B., Millman, S. E., Chen, C., Li, X., Morris, J. P., Mayle, A., Ho, Y.-J., Loizou, E., Liu, H., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2019.12.002 · Cited by 95 · see citing works
Ahmadi, S. E., Soleymani, M., Shahriyary, F., Amirzargar, M. R., Mahya, O., Fattahi, D., & Safa, M. (2023) · Cancer Gene Therapy · doi:10.1038/s41417-023-00597-z · Cited by 95 · see citing works
Tissue Engineering and Regenerative Medicine 2015: A Year in Review
Wobma, H., & Vunjak‐Novakovic, G. (2015) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2015.0535 · Cited by 92 · see citing works
Zhu, H., & Liang, C. (2019) · Bioinformatics · doi:10.1093/bioinformatics/bty1061 · Cited by 86 · see citing works
Pauli, C., Liu, Y., Rohde, C., Cui, C., Fijałkowska, D., Gerloff, D., Walter, C., Krijgsveld, J., Dugas, M., Edemir, B., et al. (2020) · Blood · doi:10.1182/blood.2019004121 · Cited by 91 · see citing works
Chronic myeloid leukemia stem cells: targeting therapeutic implications
Mojtahedi, H., Yazdanpanah, N., & Rezaei, N. (2021) · Stem Cell Research & Therapy · doi:10.1186/s13287-021-02659-1 · Cited by 91 · see citing works
CRISPR/Cas9: Transcending the Reality of Genome Editing
Chira, S., Gulei, D., Hajitou, A., Zimța, A., Cordelier, P., & Berindan‐Neagoe, I. (2017) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2017.04.001 · Cited by 88 · see citing works
Shukla, S., Cyrta, J., Murphy, D. A., Walczak, E. G., Ran, L., Agrawal, P. K., Xie, Y., Chen, Y., Wang, S., Zhan, Y., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.10.008 · Cited by 83 · see citing works
In vivo blunt-end cloning through CRISPR/Cas9-facilitated non-homologous end-joining
Geisinger, J. M., Turan, S., Hernandez, S., Spector, L. P., & Calos, M. P. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1542 · Cited by 83 · see citing works
ATF7IP regulates SETDB1 nuclear localization and increases its ubiquitination
Tsusaka, T., Shimura, C., & Shinkai, Y. (2019) · EMBO Reports · doi:10.15252/embr.201948297 · Cited by 83 · see citing works
CRISPR genome engineering and viral gene delivery: A case of mutual attraction
Schmidt, F., & Grimm, D. (2015) · Biotechnology Journal · doi:10.1002/biot.201400529 · Cited by 83 · see citing works
Anand, G. M., Megale, H. C., Murphy, S. H., Weis, T., Lin, Z., He, Y., Wang, X., Jia Liu, B., & Ramanathan, S. (2023) · Cell · doi:10.1016/j.cell.2022.12.043 · Cited by 81 · see citing works
Risk associated with off-target plant genome editing and methods for its limitation
Zhao, H., & Wolt, J. D. (2017) · Emerging Topics in Life Sciences · doi:10.1042/etls20170037 · Cited by 78 · see citing works
Chen, Y., Moutal, A., Navratilova, E., Kopruszinski, C. M., Yue, X., Ikegami, M., Chow, M., Kanazawa, I., Bellampalli, S. S., Xie, J. Y., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aay7550 · Cited by 78 · see citing works
Current approaches in CRISPR-Cas9 mediated gene editing for biomedical and therapeutic applications
Bhattacharjee, G., Gohil, N., Khambhati, K., Mani, I., Maurya, R., Karapurkar, J. K., Gohil, J., Chu, D., Vu‐Thi, H., Alzahrani, K. J., et al. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.02.005 · Cited by 78 · see citing works
Application of CRISPR/Cas9 gene editing technique in the study of cancer treatment
Jiang, C., Meng, L., Yang, B., & Luo, X. (2019) · Clinical Genetics · doi:10.1111/cge.13589 · Cited by 79 · see citing works
Efficient Gene Disruption in Cultured Primary Human Endothelial Cells by CRISPR/Cas9
Abrahimi, P., Chang, W., Kluger, M. S., Qyang, Y., Tellides, G., Saltzman, W. M., & Pober, J. S. (2015) · Circulation Research · doi:10.1161/circresaha.117.306290 · Cited by 77 · see citing works
- Authors
- Heckl, D., Kowalczyk, M. S., Yudovich, D., Belizaire, R., Puram, R. V., McConkey, M. E., Thielke, A., Aster, J. C., Regev, A., & Ebert, B. L.
- Affiliations
- Brigham and Women's Hospital (US)
- Broad Institute (US)
- Corresponding author
- Ebert, Benjamin L
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2014-06-22
- Volume
- 32
- Issue
- 9
- Pages
- 941-946
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC4160386
- OpenAlex
- W1575193685
- Cited by
- 555
- References
- 27
- Citations by year
- 2026: 14 · 2025: 29 · 2024: 28 · 2023: 58 · 2022: 58 · 2021: 58 · 2020: 61 · 2019: 51 · 2018: 54 · 2017: 61 · 2016: 38 · 2015: 39 · 2014: 5
- FWCI
- 19.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Funders
- National Heart, Lung, and Blood Institute (R01HL082945)
- National Human Genome Research Institute (P50HG006193)
- National Cancer Institute (P01CA108631, P01CA066996)
- National Institute of General Medical Sciences (T32GM007753)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- myeloid neoplasms, acute myeloid leukemia, mouse tumor model, CRISPR/Cas9 genome editing, lentiviral delivery, hematopoietic stem cells, clonal outgrowth, driver mutations, epigenetic regulators, transcription factors, cytokine signaling, cooperating mutations
- MeSH terms
- Animals, Disease Models, Animal, Bone Marrow Neoplasms, Mice, Clustered Regularly Interspaced Short Palindromic Repeats
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