Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Review Article

CRISPR-Cas9: A Potent Gene-editing Tool for the Treatment of Cancer

Author(s): Gauri Mishra, Kamakshi Srivastava, Juhi Rais, Manish Dixit, Vandana Kumari Singh and Lokesh Chandra Mishra*

Volume 24, Issue 2, 2024

Published on: 01 March, 2023

Page: [191 - 204] Pages: 14

DOI: 10.2174/1566524023666230213094308

Price: $65

Abstract

The prokaryotic adaptive immune system has clustered regularly interspaced short palindromic repeat. CRISPR-associated protein (CRISPR-Cas) genome editing systems have been harnessed. A robust programmed technique for efficient and accurate genome editing and gene targeting has been developed. Engineered cell therapy, in vivo gene therapy, animal modeling, and cancer diagnosis and treatment are all possible applications of this ground-breaking approach. Multiple genetic and epigenetic changes in cancer cells induce malignant cell growth and provide chemoresistance. The capacity to repair or ablate such mutations has enormous potential in the fight against cancer. The CRISPR-Cas9 genome editing method has recently become popular in cancer treatment research due to its excellent efficiency and accuracy. The preceding study has shown therapeutic potential in expanding our anticancer treatments by using CRISPR-Cas9 to directly target cancer cell genomic DNA in cellular and animal cancer models. In addition, CRISPR-Cas9 can combat oncogenic infections and test anticancer medicines. It may design immune cells and oncolytic viruses for cancer immunotherapeutic applications. In this review, these preclinical CRISPRCas9- based cancer therapeutic techniques are summarised, along with the hurdles and advancements in converting therapeutic CRISPR-Cas9 into clinical use. It will increase their applicability in cancer research.

[1]
Murugan K, Babu K, Sundaresan R, Rajan R, Sashital DG. The revolution continues: Newly discovered systems expand the CRISPR-Cas toolkit. Mol Cell 2017; 68(1): 15-25.
[http://dx.doi.org/10.1016/j.molcel.2017.09.007] [PMID: 28985502]
[2]
Nerys-Junior A, Braga-Dias LP, Pezzuto P, Cotta-de-Almeida V, Tanuri A. Comparison of the editing patterns and editing efficiencies of TALEN and CRISPR-Cas9 when targeting the human CCR5 gene. Genet Mol Biol 2018; 41(1): 167-79.
[http://dx.doi.org/10.1590/1678-4685-gmb-2017-0065] [PMID: 29583154]
[3]
Gutierrez-Guerrero A, Sanchez-Hernandez S, Galvani G, et al. Comparison of zinc finger nucleases versus CRISPR-specific nucleases for genome editing of the wiskott-aldrich syndrome locus. Hum Gene Ther 2018; 29(3): 366-80.
[http://dx.doi.org/10.1089/hum.2017.047] [PMID: 28922955]
[4]
Marraffini LA, Sontheimer EJ. CRISPR interference: RNA-directed adaptive immunity in bacteria and archaea. Nat Rev Genet 2010; 11(3): 181-90.
[http://dx.doi.org/10.1038/nrg2749] [PMID: 20125085]
[5]
Ishino Y, Shinagawa H, Makino K, Amemura M, Nakata A. Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. J Bacteriol 1987; 169(12): 5429-33.
[http://dx.doi.org/10.1128/jb.169.12.5429-5433.1987] [PMID: 3316184]
[6]
Nishimasu H, Ran FA, Hsu PD, et al. Crystal structure of Cas9 in complex with guide RNA and target DNA. Cell 2014; 156(5): 935-49.
[http://dx.doi.org/10.1016/j.cell.2014.02.001] [PMID: 24529477]
[7]
Zhu X, Clarke R, Puppala AK, et al. Cryo-EM structures reveal coordinated domain motions that govern DNA cleavage by Cas9. Nat Struct Mol Biol 2019; 26(8): 679-85.
[http://dx.doi.org/10.1038/s41594-019-0258-2] [PMID: 31285607]
[8]
Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 2012; 337(6096): 816-21.
[http://dx.doi.org/10.1126/science.1225829] [PMID: 22745249]
[9]
Alexandra EB, Paul DD, Ahmed AG, et al. Guide RNA functional modules direct Cas9 activity and orthogonality. Cell 2014; 56(2): 333-9.
[PMID: 25284152]
[10]
Barrangou R, Fremaux C, Deveau H, et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science 2007; 315(5819): 1709-12.
[http://dx.doi.org/10.1126/science.1138140] [PMID: 17379808]
[11]
Omer S, Alkhnbashi, Shiraz AS, et al. Characterizing leader sequences of CRISPR loci. Bioinformatics 2016; 32(17): 576-85.
[12]
Dyda F, Hickman AB. Mechanism of spacer integration links the CRISPR/Cas system to transposition as a form of mobile DNA. Mob DNA 2015; 6(1): 9.
[http://dx.doi.org/10.1186/s13100-015-0039-3] [PMID: 27408625]
[13]
Cheng K, Wilkinson M, Chaban Y, Wigley DB. A conformational switch in response to Chi converts RecBCD from phage destruction to DNA repair. Nat Struct Mol Biol 2020; 27(1): 71-7.
[http://dx.doi.org/10.1038/s41594-019-0355-2] [PMID: 31907455]
[14]
Wiktor J, van der Does M, Büller L, Sherratt DJ, Dekker C. Direct observation of end resection by RecBCD during double-stranded DNA break repair in vivo. Nucleic Acids Res 2018; 46(4): 1821-33.
[http://dx.doi.org/10.1093/nar/gkx1290] [PMID: 29294118]
[15]
Nuñez JK, Harrington LB, Kranzusch PJ, Engelman AN, Doudna JA. Foreign DNA capture during CRISPR–Cas adaptive immunity. Nature 2015; 527(7579): 535-8.
[http://dx.doi.org/10.1038/nature15760] [PMID: 26503043]
[16]
Radovcic M, Killelea T, Savitskaya E, Wettstein L, Bolt EL, Ivancic-Bace I. CRISPR-Cas adaptation in Escherichia coli requires RecBCD helicase but not nuclease activity, is independent of homologous recombination, and is antagonized by 5′ ssDNA exonucleases. Nucleic Acids Res 2018; 46(19): 10173-83.
[PMID: 30189098]
[17]
Levy A, Goren MG, Yosef I, et al. CRISPR adaptation biases explain preference for acquisition of foreign DNA. Nature 2015; 520(7548): 505-10.
[http://dx.doi.org/10.1038/nature14302] [PMID: 25874675]
[18]
Wang J, Li J, Zhao H, et al. Structural and mechanistic basis of PAM-Dependent spacer acquisition in CRISPR-Cas systems. Cell 2015; 163(4): 840-53.
[http://dx.doi.org/10.1016/j.cell.2015.10.008] [PMID: 26478180]
[19]
Nuñez JK, Lee ASY, Engelman A, Doudna JA. Integrase-mediated spacer acquisition during CRISPR–Cas adaptive immunity. Nature 2015; 519(7542): 193-8.
[http://dx.doi.org/10.1038/nature14237] [PMID: 25707795]
[20]
Kim S, Loeff L, Colombo S, Jergic S, Brouns SJJ, Joo C. Selective loading and processing of prespacers for precise CRISPR adaptation. Nature 2020; 579(7797): 141-5.
[http://dx.doi.org/10.1038/s41586-020-2018-1] [PMID: 32076262]
[21]
Bothmer A, Phadke T, Barrera LA, et al. Characterization of the interplay between DNA repair and CRISPR/Cas9-induced DNA lesions at an endogenous locus. Nat Commun 2017; 8(1): 13905.
[http://dx.doi.org/10.1038/ncomms13905] [PMID: 28067217]
[22]
Bhargava R, Sandhu M, Muk S, Lee G, Vaidehi N, Stark JM. C-NHEJ without indels is robust and requires synergistic function of distinct XLF domains. Nat Commun 2018; 9(1): 2484.
[http://dx.doi.org/10.1038/s41467-018-04867-5] [PMID: 29950655]
[23]
Chu VT, Weber T, Wefers B, et al. Increasing the efficiency of homology-directed repair for CRISPR-Cas9-induced precise gene editing in mammalian cells. Nat Biotechnol 2015; 33(5): 543-8.
[http://dx.doi.org/10.1038/nbt.3198] [PMID: 25803306]
[24]
Vartak SV, Raghavan SC. Inhibition of nonhomologous end joining to increase the specificity of CRISPR/Cas9 genome editing. FEBS J 2015; 282(22): 4289-94.
[http://dx.doi.org/10.1111/febs.13416] [PMID: 26290158]
[25]
Shen Hexi, Gary DS, Bart JPMK, Paul JJH, Sylvia de Pater. CRISPR/Cas9-induced double-strand break repair in arabidopsis nonhomologous end-joining mutants. G3 Genes|Genomes|Genetics 2017; 7(1): 193-202.
[26]
Li G, Zhang X, Zhong C, et al. Small molecules enhance CRISPR/Cas9-mediated homology-directed genome editing in primary cells. Sci Rep 2017; 7(1): 8943.
[http://dx.doi.org/10.1038/s41598-017-09306-x] [PMID: 28827551]
[27]
Simora RMC, Xing D, Bangs MR, et al. CRISPR/Cas9-mediated knock-in of alligator cathelicidin gene in a non-coding region of channel catfish genome. Sci Rep 2020; 10(1): 22271.
[http://dx.doi.org/10.1038/s41598-020-79409-5] [PMID: 33335280]
[28]
Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 2016; 533(7603): 420-4.
[http://dx.doi.org/10.1038/nature17946] [PMID: 27096365]
[29]
Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet 2002; 3(6): 415-28.
[http://dx.doi.org/10.1038/nrg816] [PMID: 12042769]
[30]
Baylin SB, Herman JG. DNA hypermethylation in tumorigenesis: epigenetics joins genetics. Trends Genet 2000; 16(4): 168-74.
[http://dx.doi.org/10.1016/S0168-9525(99)01971-X] [PMID: 10729832]
[31]
Villa R, De Santis F, Gutierrez A, Minucci S, Pelicci PG, Di Croce L. Epigenetic gene silencing in acute promyelocytic leukemia. Biochem Pharmacol 2004; 68(6): 1247-54.
[http://dx.doi.org/10.1016/j.bcp.2004.05.041] [PMID: 15313423]
[32]
Garcia-Lora A, Algarra I, Garrido F. MHC class I antigens, immune surveillance, and tumor immune escape. J Cell Physiol 2003; 195(3): 346-55.
[http://dx.doi.org/10.1002/jcp.10290] [PMID: 12704644]
[33]
Wang T, Wei JJ, Sabatini DM, Lander ES. Genetic screens in human cells using the CRISPR-Cas9 system. Science 2014; 343(6166): 80-4.
[http://dx.doi.org/10.1126/science.1246981] [PMID: 24336569]
[34]
Huang X, Zhuang C, Zhuang C, Xiong T, Li Y, Gui Y. An enhanced hTERT promoter-driven CRISPR/Cas9 system selectively inhibits the progression of bladder cancer cells. Mol Biosyst 2017; 13(9): 1713-21.
[http://dx.doi.org/10.1039/C7MB00354D] [PMID: 28702647]
[35]
Zhuang C, Zhuang C, Zhou Q, et al. Engineered CRISPR/Cas13d sensing hTERT selectively inhibits the progression of bladder cancer in vitro. Front Mol Biosci 2021; 8: 646412.
[http://dx.doi.org/10.3389/fmolb.2021.646412] [PMID: 33816560]
[36]
Aubrey BJ, Kelly GL, Kueh AJ, et al. An inducible lentiviral guide RNA platform enables the identification of tumor-essential genes and tumor-promoting mutations in vivo. Cell Rep 2015; 10(8): 1422-32.
[http://dx.doi.org/10.1016/j.celrep.2015.02.002] [PMID: 25732831]
[37]
Mali P, Yang L, Esvelt KM, et al. RNA-guided human genome engineering via Cas9. Science 2013; 339(6121): 823-6.
[http://dx.doi.org/10.1126/science.1232033] [PMID: 23287722]
[38]
Yoshiba T, Saga Y, Urabe M, et al. CRISPR/Cas9-mediated cervical cancer treatment targeting human papillomavirus E6. Oncol Lett 2019; 17(2): 2197-206.
[PMID: 30675284]
[39]
Yuen K-S, Wang Z-M, Wong N-HM, et al. Suppression of Epstein-Barr virus DNA load in latently infected nasopharyngeal carcinoma cells by CRISPR/Cas9. Virus Res 2018; 244: 296-303.
[http://dx.doi.org/10.1016/j.virusres.2017.04.019]
[40]
Mali P, Aach J, Stranges PB, et al. CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. Nat Biotechnol 2013; 31(9): 833-8.
[http://dx.doi.org/10.1038/nbt.2675] [PMID: 23907171]
[41]
Cheng AW, Wang H, Yang H, et al. Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system. Cell Res 2013; 23(10): 1163-71.
[http://dx.doi.org/10.1038/cr.2013.122] [PMID: 23979020]
[42]
Zalatan JG, Lee ME, Almeida R, et al. Engineering complex synthetic transcriptional programs with CRISPR RNA scaffolds. Cell 2015; 160(1-2): 339-50.
[http://dx.doi.org/10.1016/j.cell.2014.11.052] [PMID: 25533786]
[43]
Kostyushev D, Kostyusheva A, Brezgin S, et al. Suppressing the NHEJ pathway by DNA-PKcs inhibitor NU7026 prevents degradation of HBV cccDNA cleaved by CRISPR/Cas9. Sci Rep 2019; 9(1): 1847.
[http://dx.doi.org/10.1038/s41598-019-38526-6] [PMID: 30755668]
[44]
Marceau CD, Puschnik AS, Majzoub K, et al. Genetic dissection of Flaviviridae host factors through genome-scale CRISPR screens. Nature 2016; 535(7610): 159-63.
[http://dx.doi.org/10.1038/nature18631] [PMID: 27383987]
[45]
Campbell LA, Coke LM, Richie CT, Fortuno LV, Park AY, Harvey BK. Gesicle-mediated delivery of CRISPR/Cas9 ribonucleoprotein complex for inactivating the HIV provirus. Mol Ther 2019; 27(1): 151-63.
[http://dx.doi.org/10.1016/j.ymthe.2018.10.002] [PMID: 30389355]
[46]
Kang JG, Park JS, Ko JH, Kim YS. Regulation of gene expression by altered promoter methylation using a CRISPR/Cas9-mediated epigenetic editing system. Sci Rep 2019; 9(1): 11960.
[http://dx.doi.org/10.1038/s41598-019-48130-3] [PMID: 31427598]
[47]
Ko A, Han SY, Song J. Regulatory network of ARF in cancer development. Mol Cells 2018; 41(5): 381-9.
[PMID: 29665672]
[48]
Ishiguro A, Takahata T, Saito M, et al. Influence of methylated p15 INK4b and p16 INK4a genes on clinicopathological features in colorectal cancer. J Gastroenterol Hepatol 2006; 21(8): 1334-9.
[http://dx.doi.org/10.1111/j.1440-1746.2006.04137.x] [PMID: 16872319]
[49]
Saunderson EA, Rouault-Pierre K, Gribben JG, Ficz G. CRISPR/Cas9-targeted De Novo DNA methylation is maintained and impacts the colony forming potential of human hematopoietic CD34+ cells. Blood 2019; 134(S1): 2517.
[http://dx.doi.org/10.1182/blood-2019-130267]
[50]
Su S, Zou Z, Chen F, et al. CRISPR-Cas9-mediated disruption of PD-1 on human T cells for adoptive cellular therapies of EBV positive gastric cancer. Oncoimmunology 2016; 6(1): e1249558.
[51]
Liao Y, Chen L, Feng Y, et al. Targeting programmed cell death ligand 1 by CRISPR/Cas9 in osteosarcoma cells. Oncotarget 2017; 8(18): 30276-87.
[http://dx.doi.org/10.18632/oncotarget.16326] [PMID: 28415820]
[52]
Shi L, Meng T, Zhao Z, et al. CRISPR knock out CTLA-4 enhances the anti-tumor activity of cytotoxic T lymphocytes. Gene 2017; 636: 36-41.
[http://dx.doi.org/10.1016/j.gene.2017.09.010] [PMID: 28888577]
[53]
Manriquez-Roman C, Siegler EL, Kenderian SS. CRISPR takes the front seat in CART-Cell development. BioDrugs 2021; 35(2): 113-24.
[http://dx.doi.org/10.1007/s40259-021-00473-y] [PMID: 33638865]
[54]
Porter DL, Hwang WT, Frey NV, et al. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med 2015; 7(303): 303ra139.
[http://dx.doi.org/10.1126/scitranslmed.aac5415] [PMID: 26333935]
[55]
Kochenderfer JN, Dudley ME, Feldman SA, et al. B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor–transduced T cells. Blood 2012; 119(12): 2709-20.
[http://dx.doi.org/10.1182/blood-2011-10-384388] [PMID: 22160384]
[56]
Hillerdal V, Essand M. Chimeric antigen receptor-engineered T cells for the treatment of metastatic prostate cancer. BioDrugs 2015; 29(2): 75-89.
[http://dx.doi.org/10.1007/s40259-015-0122-9] [PMID: 25859858]
[57]
Maus MV, Haas AR, Beatty GL, et al. T cells expressing chimeric antigen receptors can cause anaphylaxis in humans. Cancer Immunol Res 2013; 1(1): 26-31.
[http://dx.doi.org/10.1158/2326-6066.CIR-13-0006]
[58]
Hu W, Zi Z, Jin Y, et al. CRISPR/Cas9-mediated PD-1 disruption enhances human mesothelin-targeted CAR T cell effector functions. Cancer Immunol Immunother 2019; 68(3): 365-77.
[http://dx.doi.org/10.1007/s00262-018-2281-2] [PMID: 30523370]
[59]
Tang N, Cheng C, Zhang X, et al. TGF-β inhibition via CRISPR promotes the long-term efficacy of CAR T cells against solid tumors. JCI Insight 2020; 5(4): e133977.
[http://dx.doi.org/10.1172/jci.insight.133977] [PMID: 31999649]
[60]
Shalem O, Sanjana NE, Hartenian E, et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 2014; 343(6166): 84-7.
[http://dx.doi.org/10.1126/science.1247005] [PMID: 24336571]
[61]
Kasap C, Elemento O, Kapoor TM. DrugTargetSeqR: a genomics- and CRISPR-Cas9–based method to analyze drug targets. Nat Chem Biol 2014; 10(8): 626-8.
[http://dx.doi.org/10.1038/nchembio.1551] [PMID: 24929528]
[62]
Kim D, Bae S, Park J, et al. Digenome-seq: genome-wide profiling of CRISPR-Cas9 off-target effects in human cells. Nat Methods 2015; 12(3): 237-43.
[http://dx.doi.org/10.1038/nmeth.3284] [PMID: 25664545]
[63]
Charlesworth CT, Deshpande PS, Dever DP, et al. Identification of preexisting adaptive immunity to Cas9 proteins in humans. Nat Med 2019; 25(2): 249-54.
[http://dx.doi.org/10.1038/s41591-018-0326-x] [PMID: 30692695]
[64]
Edward A, Joseph A, Fraietta MD, et al. June CRISPR-engineered T cells in patients withrefractory cancer. Science 2020; 367(6481)
[65]
Ferdosi SR, Ewaisha R, Moghadam F, et al. Multifunctional CRISPR-Cas9 with engineered immunosilenced human T cell epitopes. Nat Commun 2019; 10(1): 1842.
[http://dx.doi.org/10.1038/s41467-019-09693-x] [PMID: 31015529]
[66]
Enache OM, Rendo V, Abdusamad M, et al. Cas9 activates the p53 pathway and selects for p53-inactivating mutations. Nat Genet 2020; 52(7): 662-8.
[http://dx.doi.org/10.1038/s41588-020-0623-4] [PMID: 32424350]
[67]
Ghaemi A, Bagheri E, Abnous K, Taghdisi SM, Ramezani M, Alibolandi M. CRISPR-cas9 genome editing delivery systems for targeted cancer therapy. Life Sci 2021; 267: 118969.
[http://dx.doi.org/10.1016/j.lfs.2020.118969]
[68]
Ray SK, Mukherjee S. Genome editing with CRISPR-Cas9: A budding biological contrivance for colorectal carcinoma research and its perspective in molecular medicine. Curr Mol Med 2021; 21(6): 462-75.
[http://dx.doi.org/10.2174/1566524020666201119143943] [PMID: 33213345]
[69]
Koppes EA, Redel BK, Johnson MA, et al. A porcine model of phenylketonuria generated by CRISPR/Cas9 genome editing. JCI Insight 2020; 5(20): e141523.
[http://dx.doi.org/10.1172/jci.insight.141523] [PMID: 33055427]
[70]
Marangi M, Pistritto G. Innovative therapeutic strategies for cystic fibrosis: Moving forward to CRISPR technique. Front Pharmacol 2018; 9: 396.
[http://dx.doi.org/10.3389/fphar.2018.00396] [PMID: 29731717]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy