The Applications of Genome Editing in the Management of Cancer: A Narrative Overview

Ismail Ibrahim Al-Janabi

doi:10.54133/ajms.v6i1.503

Authors

Ismail Ibrahim Al-Janabi Retired Academic, Freelance Consultant Pharmacist and Science Writer, Epsom, Surrey, UK

DOI:

https://doi.org/10.54133/ajms.v6i1.503

Keywords:

Cancer, CRISPR/Cas9 gene-editing, genome-editing

Abstract

Objective: To provide an overview of the status of applying genome editing, particularly CRISPR/Cas9, in the management of cancer. Method: Several search tools were consulted in the preparation of this manuscript to obtain peer-reviewed articles using the given evaluation and selection criteria. Main points: CRISPR/Cas9 and its associated variants stood out as the technology of choice for manipulating cancer cells and managing the disease. This genome-editing technology can positively contribute to the elucidation of the roles of cancer genes, establish animal models to study the disease, and therapeutically empower the development of next-generation immunotherapies. Conclusions: The manipulation of the human genome using CRISPR/Cas9 to treat cancer has only recently begun. Several clinical trials are ongoing, and the results are eagerly awaited. In the meantime, improvements and advancements in genome editing are being developed at a rapid pace to take advantage of this evolving technology.

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References

Hsu PD, Lander ES, Zhang F. Development and applications of CRISPR-Cas9 for genome engineering. Cell. 2014;157(6):1262-1278. doi: 10.1016/j.cell.2014.05.010.

Akram F, Sahreen S, Aamir F, Haq IU, Malik K, Naseem IM, et al. An insight into modern targeted genome-editing technologies with a special focus on CRISPR/Cas9 and its applications. Mol Biotechnol. 2023;65(2):227-242. doi: 10.1007/s12033-022-00501-4.

Khan SH. Genome-editing technologies: Concept, pros, and cons of various genome-editing techniques and bioethical concerns for clinical application. Mol Ther Nucleic Acids. 2019;16:326-334. doi: 10.1016/j.omtn.2019.02.027.

Gaj T, Gersbach CA, Barbas CF. ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol. 2013;31(7):397-405. doi: 10.1016/j.tibtech.2013.04.004.

Urnov FD, Rebar EJ, Holmes MC, Zhang HS, Gregory PD. Genome editing with engineered zinc finger nucleases. Nat Rev Genet. 2010;11(9):636-646. doi: 10.1038/nrg2842.

Joung JK, Sander JD. TALENs: a widely applicable technology for targeted genome editing. Nat Rev Mol Cell Biol. 2013;14(1):49-55. doi: 10.1038/nrm3486.

Doudna JA, Charpentier E. Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science. 2014;346(6213):1258096. doi: 10.1126/science.1258096.

Nasrallah A, Sulpice E, Kobaisi F, Gidrol X, Rachidi W. CRISPR-Cas9 technology for the creation of biological avatars capable of modeling and treating pathologies: From discovery to the latest improvements. Cells. 2022;11(22):3615. doi: 10.3390/cells11223615.

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):5429-5433. doi: 10.1128/jb.169.12.5429-5433.1987.

Mojica FJ, Juez G, Rodríguez-Valera F. Transcription at different salinities of Haloferax mediterranei sequences adjacent to partially modified PstI sites. Mol Microbiol. 1993;9(3):613-621. doi: 10.1111/j.1365-2958.1993.tb01721.x.

Jansen R, Embden JD, Gaastra W, Schouls LM. Identification of genes that are associated with DNA repeats in prokaryotes. Mol Microbiol. 2002;43(6):1565-1575. doi: 10.1046/j.1365-2958.2002.02839.x.

Makarova KS, Aravind L, Grishin NV, Rogozin IB, Koonin EV. A DNA repair system specific for thermophilic Archaea and bacteria predicted by genomic context analysis. Nucleic Acids Res. 2002;30(2):482-496. doi: 10.1093/nar/30.2.482.

Heler R, Marraffini LA, Bikard D. Adapting to new threats: the generation of memory by CRISPR-Cas immune systems. Mol Microbiol. 2014;93(1):1-9. doi: 10.1111/mmi.12640.

Marraffini LA. CRISPR-Cas immunity in prokaryotes. Nature. 2015;526(7571):55-61. doi: 10.1038/nature15386.

Mojica FJ, Rodriguez-Valera F. The discovery of CRISPR in archaea and bacteria. FEBS J. 2016;283(17):3162-3169. doi: 10.1111/febs.13766.

Charpentier E, Doudna JA. Biotechnology: Rewriting a genome. Nature. 2013;495(7439):50-51. doi: 10.1038/495050a.

Jiang F, Doudna JA. CRISPR-Cas9 structures and mechanisms. Annu Rev Biophys. 2017;46:505-529. doi: 10.1146/annurev-biophys-062215-010822.

Li C, Brant E, Budak H, Zhang B. CRISPR/Cas: A Nobel Prize award-winning precise genome editing technology for gene therapy and crop improvement. J Zhejiang Univ Sci B. 2021;22(4):253-284. doi: 10.1631/jzus.B2100009.

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):816-821. doi: 10.1126/science.1225829.

Nishimasu H, Ran FA, Hsu PD, Konermann S, Shehata SI, Dohmae N, et al. Crystal structure of Cas9 in complex with guide RNA and target DNA. Cell. 2014;156(5):935-49. doi: 10.1016/j.cell.2014.02.001.

Yang X, Zhang B. A review on CRISPR/Cas: a versatile tool for cancer screening, diagnosis, and clinic treatment. Funct Integr Genomics. 2023;23(2):182. doi: 10.1007/s10142-023-01117-w.

Garneau JE, Dupuis MÈ, Villion M, Romero DA, Barrangou R, Boyaval P, et al. The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Nature. 2010;468(7320):67-71. doi: 10.1038/nature09523.

Gasiunas G, Barrangou R, Horvath P, Siksnys V. Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Proc Natl Acad Sci U S A. 2012;109(39):E2579-2586. doi: 10.1073/pnas.1208507109.

Katti A, Diaz BJ, Caragine CM, Sanjana NE, Dow LE. CRISPR in cancer biology and therapy. Nat Rev Cancer. 2022;22(5):259-279. doi: 10.1038/s41568-022-00441-w.

Anders C, Niewoehner O, Duerst A, Jinek M. Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease. Nature. 2014;513(7519):569-573. doi: 10.1038/nature13579.

Heyer WD, Ehmsen KT, Liu J. Regulation of homologous recombination in eukaryotes. Annu Rev Genet. 2010;44:113-139. doi: 10.1146/annurev-genet-051710-150955.

Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, et al. Multiplex genome engineering using CRISPR/Cas systems. Science. 2013;339(6121):819-823. doi: 10.1126/science.1231143.

Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, et al. RNA-guided human genome engineering via Cas9. Science. 2013;339(6121):823-826. doi: 10.1126/science.1232033.

Ventura A, Dow LE. Modelling cancer in the CRISPR era. Annu Rev Cancer Biol. 2018, 2:111-131.

Zetsche B, Gootenberg JS, Abudayyeh OO, Slaymaker IM, Makarova KS, Essletzbichler P, et al. Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. Cell. 2015;163(3):759-771. doi: 10.1016/j.cell.2015.09.038.

Safari F, Zare K, Negahdaripour M, Barekati-Mowahed M, Ghasemi Y. CRISPR Cpf1 proteins: structure, function and implications for genome editing. Cell Biosci. 2019;9:36. doi: 10.1186/s13578-019-0298-7.

Pickar-Oliver A, Gersbach CA. The next generation of CRISPR-Cas technologies and applications. Nat Rev Mol Cell Biol. 2019;20(8):490-507. doi: 10.1038/s41580-019-0131-5.

Hendriks D, Clevers H, Artegiani B. CRISPR-Cas Tools and their application in genetic engineering of human stem cells and organoids. Cell Stem Cell. 2020 Nov 5;27(5):705-731. doi: 10.1016/j.stem.2020.10.014.

Ran FA, Cong L, Yan WX, Scott DA, Gootenberg JS, Kriz AJ, et al. In vivo genome editing using Staphylococcus aureus Cas9. Nature. 2015;520(7546):186-191. doi: 10.1038/nature14299.

Kim E, Koo T, Park SW, Kim D, Kim K, Cho HY, et al. In vivo genome editing with a small Cas9 orthologue derived from Campylobacter jejuni. Nat Commun. 2017;8:14500. doi: 10.1038/ncomms14500.

Abudayyeh OO, Gootenberg JS, Konermann S, Joung J, Slaymaker IM, Cox DB, et al. C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector. Science. 2016;353(6299):aaf5573. doi: 10.1126/science.aaf5573.

East-Seletsky A, O'Connell MR, Knight SC, Burstein D, Cate JH, Tjian R, et al. Two distinct RNase activities of CRISPR-C2c2 enable guide-RNA processing and RNA detection. Nature. 2016;538(7624):270-273. doi: 10.1038/nature19802.

Rees HA, Liu DR. Base editing: precision chemistry on the genome and transcriptome of living cells. Nat Rev Genet. 2018;19(12):770-788. doi: 10.1038/s41576-018-0059-1.

Anzalone AV, Randolph PB, Davis JR, Sousa AA, Koblan LW, Levy JM, et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature. 2019;576(7785):149-157. doi: 10.1038/s41586-019-1711-4.

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):420-424. doi: 10.1038/nature17946.

Gaudelli NM, Komor AC, Rees HA, Packer MS, Badran AH, Bryson DI, et al. Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature. 2017;551(7681):464-471. doi: 10.1038/nature24644.

Landrum MJ, Lee JM, Benson M, Brown G, Chao C, Chitipiralla S, et al. ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Res. 2016;44(D1):D862-868. doi: 10.1093/nar/gkv1222.

Anzalone AV, Koblan LW, Liu DR. Genome editing with CRISPR-Cas nucleases, base editors, transposases and prime editors. Nat Biotechnol. 2020;38(7):824-844. doi: 10.1038/s41587-020-0561-9.

Zhao Z, Shang P, Mohanraju P, Geijsen N. Prime editing: advances and therapeutic applications. Trends Biotechnol. 2023;41(8):1000-1012. doi: 10.1016/j.tibtech.2023.03.004.

Chow RD, Chen JS, Shen J, Chen S. A web tool for the design of prime-editing guide RNAs. Nat Biomed Eng. 2021;5(2):190-194. doi: 10.1038/s41551-020-00622-8.

Hsu JY, Grünewald J, Szalay R, Shih J, Anzalone AV, Lam KC, et al. PrimeDesign software for rapid and simplified design of prime editing guide RNAs. Nat Commun. 2021;12(1):1034. doi: 10.1038/s41467-021-21337-7.

Qi LS, Larson MH, Gilbert LA, Doudna JA, Weissman JS, Arkin AP, et al. Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell. 2013;152(5):1173-1183. doi: 10.1016/j.cell.2013.02.022.

Zhang B, Farwell MA. microRNAs: a new emerging class of players for disease diagnostics and gene therapy. J Cell Mol Med. 2008;12(1):3-21. doi: 10.1111/j.1582-4934.2007.00196.x.

Abudayyeh OO, Gootenberg JS, Essletzbichler P, Han S, Joung J, Belanto JJ, et al. RNA targeting with CRISPR-Cas13. Nature. 2017;550(7675):280-284. doi: 10.1038/nature24049.

Cox DBT, Gootenberg JS, Abudayyeh OO, Franklin B, Kellner MJ, Joung J, et al. RNA editing with CRISPR-Cas13. Science. 2017;358(6366):1019-1027. doi: 10.1126/science.aaq0180.

Shojaei Baghini S, Gardanova ZR, Abadi SAH, Zaman BA, İlhan A, Shomali N, et al. CRISPR/Cas9 application in cancer therapy: a pioneering genome editing tool. Cell Mol Biol Lett. 2022;27(1):35. doi: 10.1186/s11658-022-00336-6.

Chira S, Nutu A, Isacescu E, Bica C, Pop L, Ciocan C, et al. Genome editing approaches with CRISPR/Cas9 for cancer treatment: Critical appraisal of preclinical and clinical utility, challenges, and future research. Cells. 2022;11(18):2781. doi: 10.3390/cells11182781.

Mitra S, Sarker J, Mojumder A, Shibbir TB, Das R, Emran TB, et al. Genome editing and cancer: How far has research moved forward on CRISPR/Cas9? Biomed Pharmacother. 2022;150:113011. doi: 10.1016/j.biopha.2022.113011.

Rabaan AA, AlSaihati H, Bukhamsin R, Bakhrebah MA, Nassar MS, Alsaleh AA, et al. Application of CRISPR/Cas9 technology in cancer treatment: A future direction. Curr Oncol. 2023;30(2):1954-1976. doi: 10.3390/curroncol30020152.

My cancer genome. https://www.mycancergenome.org/content/alteration/tp53-mutation/. Last accessed on 14.11.2023.

Tp53 gene. https://ghr.nlm.nih.gov/gene/tp53#sources-forpage. Last accessed on 14.11.2023.

IARC TP53 Database. https://p53.iarc.fr/tp53somaticmutations.aspx. Last accessed 14.11.2023.

Zhu J, Sammons MA, Donahue G, Dou Z, Vedadi M, Getlik M, et al. Gain-of-function p53 mutants co-opt chromatin pathways to drive cancer growth. Nature. 2015;525(7568):206-211. doi: 10.1038/nature15251.

Pitolli C, Wang Y, Mancini M, Shi Y, Melino G, Amelio I. Do mutations turn p53 into an oncogene? Int J Mol Sci. 2019;20(24):6241. doi: 10.3390/ijms20246241.

Chira S, Gulei D, Hajitou A, Berindan-Neagoe I. Restoring the p53 'Guardian' phenotype in p53-deficient tumor cells with CRISPR/Cas9. Trends Biotechnol. 2018;36(7):653-660. doi: 10.1016/j.tibtech.2018.01.014.

Zhan H, Xie H, Zhou Q, Liu Y, Huang W. Synthesizing a genetic sensor based on CRISPR-Cas9 for specifically killing p53-deficient cancer cells. ACS Synth Biol. 2018;7(7):1798-1807. doi: 10.1021/acssynbio.8b00202.

Kim W, Lee S, Kim HS, Song M, Cha YH, Kim YH, et al. Targeting mutant KRAS with CRISPR-Cas9 controls tumor growth. Genome Res. 2018;28(3):374-382. doi: 10.1101/gr.223891.117.

Feng W, Zhang H, Le XC. Signal amplification by the trans-cleavage activity of CRISPR-Cas systems: Kinetics and performance. Anal Chem. 2023;95(1):206-217. doi: 10.1021/acs.analchem.2c04555.

Gootenberg JS, Abudayyeh OO, Lee JW, Essletzbichler P, Dy AJ, Joung J, et al. Nucleic acid detection with CRISPR-Cas13a/C2c2. Science. 2017;356(6336):438-442. doi: 10.1126/science.aam9321.

Chen JS, Ma E, Harrington LB, Da Costa M, Tian X, Palefsky JM, et al. CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase activity. Science. 2018;360(6387):436-439. doi: 10.1126/science.aar6245.

Li SY, Cheng QX, Wang JM, Li XY, Zhang ZL, Gao S, et al. CRISPR-Cas12a-assisted nucleic acid detection. Cell Discov. 2018;4:20. doi: 10.1038/s41421-018-0028-z.

Gilbert LA, Horlbeck MA, Adamson B, Villalta JE, Chen Y, Whitehead EH, et al. Genome-scale CRISPR-mediated control of gene repression and activation. Cell. 2014;159(3):647-661. doi: 10.1016/j.cell.2014.09.029.

Koike-Yusa H, Li Y, Tan EP, Velasco-Herrera Mdel C, Yusa K. Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library. Nat Biotechnol. 2014;32(3):267-273. doi: 10.1038/nbt.2800.

Shalem O, Sanjana NE, Hartenian E, Shi X, Scott DA, Mikkelson T, et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science. 2014;343(6166):84-87. doi: 10.1126/science.1247005.

Hart T, Chandrashekhar M, Aregger M, Steinhart Z, Brown KR, MacLeod G, et al. High-resolution CRISPR screens reveal fitness genes and genotype-specific cancer liabilities. Cell. 2015;163(6):1515-1526. doi: 10.1016/j.cell.2015.11.015.

Wang T, Birsoy K, Hughes NW, Krupczak KM, Post Y, Wei JJ, et al. Identification and characterization of essential genes in the human genome. Science. 2015;350(6264):1096-1101. doi: 10.1126/science.aac7041.

Mandegar MA, Huebsch N, Frolov EB, Shin E, Truong A, Olvera MP, et al. CRISPR interference efficiently induces specific and reversible gene silencing in human iPSCs. Cell Stem Cell. 2016;18(4):541-553. doi: 10.1016/j.stem.2016.01.022.

Konermann S, Brigham MD, Trevino AE, Joung J, Abudayyeh OO, Barcena C, et al. Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature. 2015;517(7536):583-588. doi: 10.1038/nature14136.

Fellmann C, Gowen BG, Lin PC, Doudna JA, Corn JE. Cornerstones of CRISPR-Cas in drug discovery and therapy. Nat Rev Drug Discov. 2017;16(2):89-100. doi: 10.1038/nrd.2016.238.

Maus MV, Grupp SA, Porter DL, June CH. Antibody-modified T cells: CARs take the front seat for hematologic malignancies. Blood. 2014;123(17):2625-2635. doi: 10.1182/blood-2013-11-492231.

Al-Janabi I. Response challenges to cancer immunotherapies. Al-Rafidain J Med Sci. 2022;2:51-80. doi: 10.54133/ajms.v2i.65.

Ren J, Liu X, Fang C, Jiang S, June CH, Zhao Y. Multiplex genome editing to generate universal CAR T cells resistant to PD1 inhibition. Clin Cancer Res. 2017;23(9):2255-2266. doi: 10.1158/1078-0432.CCR-16-1300.

Liu X, Zhang Y, Cheng C, Cheng AW, Zhang X, Li N, et al. CRISPR-Cas9-mediated multiplex gene editing in CAR-T cells. Cell Res. 2017;27(1):154-157. doi: 10.1038/cr.2016.142.

Stadtmauer EA, Fraietta JA, Davis MM, Cohen AD, Weber KL, Lancaster E, et al. CRISPR-engineered T cells in patients with refractory cancer. Science. 2020;367(6481):eaba7365. doi: 10.1126/science.aba7365.