1932
0

Annual Review of Cancer Biology

Volume 9, 2025

Awakening the Genome: CRISPR Activation to Unravel the Origin and Vulnerabilities of Cancer

  • John E. La Marca1,2,3,4,*, Sarah T. Diepstraten3,4,*, Gemma L. Kelly3,4 and Marco J. Herold1,2,3,4
  • 1Genome Engineering and Cancer Modelling Program, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia; email: [email protected] 2School of Cancer Medicine, La Trobe University, Bundoora, Victoria, Australia 3The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia 4Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia
    * These authors contributed equally to this article
  • Vol. 9:141-159 (Volume publication date April 2025)
  • First published as a Review in Advance on November 12, 2024
  • Copyright © 2025 by the author(s).
    This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.

Abstract

CRISPR activation (CRISPRa) co-opts nuclease-dead Cas-molecule DNA-binding capabilities to direct transcriptional activators to specific loci, driving gene expression. CRISPRa technology has advanced rapidly in the past few years, and it is now applicable to a wide range of biological questions, including the study of cancer. In this review, we discuss the different forms of CRISPRa technologies, their in vitro and in vivo applications, and recent studies that have used CRISPRa in their cancers of choice. We further discuss the different CRISPRa tools that are available, including mouse models and single-guide RNA libraries. Finally, we examine the maturation of CRISPRa, as its potential therapeutic applications are beginning to be explored.

Keyword(s): activation, cancer, CRISPR, library, mouse, screen
Loading

Article metrics loading...

/content/journals/10.1146/annurev-cancerbio-062624-104149
2025-04-11
2025-06-15
Loading full text...

Full text loading...

/deliver/fulltext/cancerbio/9/1/annurev-cancerbio-062624-104149.html?itemId=/content/journals/10.1146/annurev-cancerbio-062624-104149&mimeType=html&fmt=ahah

Literature Cited

  1. Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, et al. 2007.. CRISPR provides acquired resistance against viruses in prokaryotes. . Science 315::1709–12
     [Crossref] [Google Scholar]
  2. Beck CR, Collier P, Macfarlane C, Malig M, Kidd JM, et al. 2010.. LINE-1 retrotransposition activity in human genomes. . Cell 141::1159–70
     [Crossref] [Google Scholar]
  3. Bester AC, Lee JD, Chavez A, Lee YR, Nachmani D, et al. 2018.. An integrated genome-wide CRISPRa approach to functionalize lncRNAs in drug resistance. . Cell 173::649–64.e20
     [Crossref] [Google Scholar]
  4. Bikard D, Jiang W, Samai P, Hochschild A, Zhang F, Marraffini LA. 2013.. Programmable repression and activation of bacterial gene expression using an engineered CRISPR-Cas system. . Nucleic Acids Res. 41::7429–37
     [Crossref] [Google Scholar]
  5. Binan L, Danquah S, Valakh V, Simonton B, Bezney J, et al. 2023.. Simultaneous CRISPR screening and spatial transcriptomics reveals intracellular, intercellular, and functional transcriptional circuits. . bioRxiv 2023.11.30.569494. https://doi.org/10.1101/2023.11.30.569494
  6. Bolotin A, Quinquis B, Sorokin A, Ehrlich SD. 2005.. Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. . Microbiology 151::2551–61
     [Crossref] [Google Scholar]
  7. Brouns SJ, Jore MM, Lundgren M, Westra ER, Slijkhuis RJ, et al. 2008.. Small CRISPR RNAs guide antiviral defense in prokaryotes. . Science 321::960–64
     [Crossref] [Google Scholar]
  8. Budkova Z, Sigurdardottir AK, Briem E, Bergthorsson JT, Sigurdsson S, et al. 2020.. Expression of ncRNAs on the DLK1-DIO3 locus is associated with basal and mesenchymal phenotype in breast epithelial progenitor cells. . Front. Cell Dev. Biol. 8::461
     [Crossref] [Google Scholar]
  9. Chavez A, Scheiman J, Vora S, Pruitt BW, Tuttle M, et al. 2015.. Highly efficient Cas9-mediated transcriptional programming. . Nat. Methods 12::326–28
     [Crossref] [Google Scholar]
  10. Chavez A, Tuttle M, Pruitt BW, Ewen-Campen B, Chari R, et al. 2016.. Comparison of Cas9 activators in multiple species. . Nat. Methods 13::563–67
     [Crossref] [Google Scholar]
  11. Cheng AW, Wang H, Yang H, Shi L, Katz Y, et al. 2013.. Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system. . Cell Res. 23::1163–71
     [Crossref] [Google Scholar]
  12. Chong ZS, Ohnishi S, Yusa K, Wright GJ. 2018.. Pooled extracellular receptor-ligand interaction screening using CRISPR activation. . Genome Biol. 19:: 205. Erratum . 2022.. Genome Biol. 23::224
     [Google Scholar]
  13. Cong L, Ran FA, Cox D, Lin S, Barretto R, et al. 2013.. Multiplex genome engineering using CRISPR/Cas systems. . Science 339::819–23
     [Crossref] [Google Scholar]
  14. Cui X, Zhang C, Xu Z, Wang S, Li X, et al. 2022.. Dual CRISPR interference and activation for targeted reactivation of X-linked endogenous FOXP3 in human breast cancer cells. . Mol. Cancer 21::38
     [Crossref] [Google Scholar]
  15. Dale KL, Armond JW, Hynds RE, Vladimirou E. 2022.. Modest increase of KIF11 expression exposes fragilities in the mitotic spindle, causing chromosomal instability. . J. Cell Sci. 135::jcs260031
     [Crossref] [Google Scholar]
  16. Dammert MA, Brägelmann J, Olsen RR, Böhm S, Monhasery N, et al. 2019.. MYC paralog-dependent apoptotic priming orchestrates a spectrum of vulnerabilities in small cell lung cancer. . Nat. Commun. 10::3485
     [Crossref] [Google Scholar]
  17. Das S, Bano S, Kapse P, Kundu GC. 2022.. CRISPR based therapeutics: a new paradigm in cancer precision medicine. . Mol. Cancer 21::85
     [Crossref] [Google Scholar]
  18. Datlinger P, Rendeiro AF, Schmidl C, Krausgruber T, Traxler P, et al. 2017.. Pooled CRISPR screening with single-cell transcriptome readout. . Nat. Methods 14::297–301
     [Crossref] [Google Scholar]
  19. Deaner M, Mejia J, Alper HS. 2017.. Enabling graded and large-scale multiplex of desired genes using a dual-mode dCas9 activator in Saccharomyces cerevisiae. . ACS Synth. Biol. 6::1931–43
     [Crossref] [Google Scholar]
  20. Deltcheva E, Chylinski K, Sharma CM, Gonzales K, Chao Y, et al. 2011.. CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. . Nature 471::602–7
     [Crossref] [Google Scholar]
  21. Deng Y, Diepstraten ST, Potts MA, Giner G, Trezise S, et al. 2022.. Generation of a CRISPR activation mouse that enables modelling of aggressive lymphoma and interrogation of venetoclax resistance. . Nat. Commun. 13::4739
     [Crossref] [Google Scholar]
  22. Deveau H, Barrangou R, Garneau JE, Labonté J, Fremaux C, et al. 2008.. Phage response to CRISPR-encoded resistance in Streptococcus thermophilus. . J. Bacteriol. 190::1390–400
     [Crossref] [Google Scholar]
  23. Dhainaut M, Rose SA, Akturk G, Wroblewska A, Nielsen SR, et al. 2022.. Spatial CRISPR genomics identifies regulators of the tumor microenvironment. . Cell 185::1223–39.e20
     [Crossref] [Google Scholar]
  24. Ding G, Yu S, Cheng S, Li G, Yu Y. 2016.. Androgen receptor (AR) promotes male bladder cancer cell proliferation and migration via regulating CD24 and VEGF. . Am. J. Transl. Res. 8::578–87
     [Google Scholar]
  25. Ding W, Wang C, Narita Y, Wang H, Leong MML, et al. 2022.. The Epstein-Barr virus enhancer interaction landscapes in virus-associated cancer cell lines. . J. Virol. 96::e0073922
     [Crossref] [Google Scholar]
  26. Dixit A, Parnas O, Li B, Chen J, Fulco CP, et al. 2016.. Perturb-Seq: dissecting molecular circuits with scalable single-cell RNA profiling of pooled genetic screens. . Cell 167::1853–66.e17
     [Crossref] [Google Scholar]
  27. Doench JG, Fusi N, Sullender M, Hegde M, Vaimberg EW, et al. 2016.. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9. . Nat. Biotechnol. 34::184–91
     [Crossref] [Google Scholar]
  28. Ebright RY, Lee S, Wittner BS, Niederhoffer KL, Nicholson BT, et al. 2020.. Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis. . Science 367::1468–73
     [Crossref] [Google Scholar]
  29. Farzadfard F, Perli SD, Lu TK. 2013.. Tunable and multifunctional eukaryotic transcription factors based on CRISPR/Cas. . ACS Synth. Biol. 2::604–13
     [Crossref] [Google Scholar]
  30. Fonfara I, Richter H, Bratovič M, Le Rhun A, Charpentier E. 2016.. The CRISPR-associated DNA-cleaving enzyme Cpf1 also processes precursor CRISPR RNA. . Nature 532::517–21
     [Crossref] [Google Scholar]
  31. Garneau JE, Dupuis M, Villion M, Romero DA, Barrangou R, et al. 2010.. The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. . Nature 468::67–71
     [Crossref] [Google Scholar]
  32. Gasiunas G, Barrangou R, Horvath P, Siksnys V. 2012.. Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. . PNAS 109::E2579–86
     [Crossref] [Google Scholar]
  33. Gemberling MP, Siklenka K, Rodriguez E, Tonn-Eisinger KR, Barrera A, et al. 2021.. Transgenic mice for in vivo epigenome editing with CRISPR-based systems. . Nat. Methods 18::965–74
     [Crossref] [Google Scholar]
  34. Gilbert LA, Horlbeck MA, Adamson B, Villalta JE, Chen Y, et al. 2014.. Genome-scale CRISPR-mediated control of gene repression and activation. . Cell 159::647–61
     [Crossref] [Google Scholar]
  35. Gilbert LA, Larson MH, Morsut L, Liu Z, Brar GA, et al. 2013.. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. . Cell 154::442–51
     [Crossref] [Google Scholar]
  36. González-Vallinas M, Rodríguez-Paredes M, Albrecht M, Sticht C, Stichel D, et al. 2018.. Epigenetically regulated chromosome 14q32 miRNA cluster induces metastasis and predicts poor prognosis in lung adenocarcinoma patients. . Mol. Cancer Res. 16::390–402
     [Crossref] [Google Scholar]
  37. Green M, Schuetz TJ, Sullivan EK, Kingston RE. 1995.. A heat shock-responsive domain of human HSF1 that regulates transcription activation domain function. . Mol. Cell. Biol. 15::3354–62
     [Crossref] [Google Scholar]
  38. Guardia T, Zhang Y, Thompson KN, Lee SJ, Martin SS, et al. 2023.. OBSCN restoration via OBSCN-AS1 long-noncoding RNA CRISPR-targeting suppresses metastasis in triple-negative breast cancer. . PNAS 120::e2215553120
     [Crossref] [Google Scholar]
  39. Hardwick JM, Tse L, Applegren N, Nicholas J, Veliuona MA. 1992.. The Epstein-Barr virus R transactivator (Rta) contains a complex, potent activation domain with properties different from those of VP16. . J. Virol. 66::5500–8
     [Crossref] [Google Scholar]
  40. Heidersbach AJ, Dorighi KM, Gomez JA, Jacobi AM, Haley B. 2023.. A versatile, high-efficiency platform for CRISPR-based gene activation. . Nat. Commun. 14::902
     [Crossref] [Google Scholar]
  41. Hermans PW, van Soolingen D, Bik EM, de Haas PE, Dale JW, van Embden JD. 1991.. Insertion element IS987 from Mycobacterium bovis BCG is located in a hot-spot integration region for insertion elements in Mycobacterium tuberculosis complex strains. . Infect. Immun. 59::2695–705
     [Crossref] [Google Scholar]
  42. Hill AJ, McFaline-Figueroa JL, Starita LM, Gasperini MJ, Matreyek KA, et al. 2018.. On the design of CRISPR-based single-cell molecular screens. . Nat. Methods 15::271–74
     [Crossref] [Google Scholar]
  43. Hilton IB, D'Ippolito AM, Vockley CM, Thakore PI, Crawford GE, et al. 2015.. Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. . Nat. Biotechnol. 33::510–17
     [Crossref] [Google Scholar]
  44. Horlbeck MA, Gilbert LA, Villalta JE, Adamson B, Pak RA, et al. 2016.. Compact and highly active next-generation libraries for CRISPR-mediated gene repression and activation. . eLife 5::e19760
     [Crossref] [Google Scholar]
  45. Hu J, Lei Y, Wong WK, Liu S, Lee KC, et al. 2014.. Direct activation of human and mouse Oct4 genes using engineered TALE and Cas9 transcription factors. . Nucleic Acids Res. 42::4375–90
     [Crossref] [Google Scholar]
  46. Huang YH, Su J, Lei Y, Brunetti L, Gundry MC, et al. 2017.. DNA epigenome editing using CRISPR-Cas SunTag-directed DNMT3A. . Genome Biol. 18::176
     [Crossref] [Google Scholar]
  47. Hunt C, Hartford SA, White D, Pefanis E, Hanna T, et al. 2021.. Tissue-specific activation of gene expression by the Synergistic Activation Mediator (SAM) CRISPRa system in mice. . Nat. Commun. 12::2770
     [Crossref] [Google Scholar]
  48. Idres YM, Lai AJ, McMillan NAJ, Idris A. 2023.. Hyperactivation of p53 using CRISPRa kills human papillomavirus-driven cervical cancer cells. . Virus Genes 59::312–16
     [Crossref] [Google Scholar]
  49. Ishino Y, Shinagawa H, Makino K, Amemura M, Nakata A. 1987.. Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. . J. Bacteriol. 169::5429–33
     [Crossref] [Google Scholar]
  50. Jaitin DA, Weiner A, Yofe I, Lara-Astiaso D, Keren-Shaul H, et al. 2016.. Dissecting immune circuits by linking CRISPR-pooled screens with single-cell RNA-Seq. . Cell 167::1883–96.e15
     [Crossref] [Google Scholar]
  51. Jansen R, Embden JD, Gaastra W, Schouls LM. 2002.. Identification of genes that are associated with DNA repeats in prokaryotes. . Mol. Microbiol. 43::1565–75
     [Crossref] [Google Scholar]
  52. Jia Y, Xu RG, Ren X, Ewen-Campen B, Rajakumar R, et al. 2018.. Next-generation CRISPR/Cas9 transcriptional activation in Drosophila using flySAM. . PNAS 115::4719–24
     [Crossref] [Google Scholar]
  53. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. 2012.. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. . Science 337::816–21
     [Crossref] [Google Scholar]
  54. Joung J, Engreitz JM, Konermann S, Abudayyeh OO, Verdine VK, et al. 2017a.. Genome-scale activation screen identifies a lncRNA locus regulating a gene neighbourhood. . Nature 548::343–46
     [Crossref] [Google Scholar]
  55. Joung J, Kirchgatterer PC, Singh A, Cho JH, Nety SP, et al. 2022.. CRISPR activation screen identifies BCL-2 proteins and B3GNT2 as drivers of cancer resistance to T cell-mediated cytotoxicity. . Nat. Commun. 13::1606
     [Crossref] [Google Scholar]
  56. Joung J, Konermann S, Gootenberg JS, Abudayyeh OO, Platt RJ, et al. 2017b.. Genome-scale CRISPR-Cas9 knockout and transcriptional activation screening. . Nat. Protoc. 12::828–63
     [Crossref] [Google Scholar]
  57. Kearns NA, Genga RM, Enuameh MS, Garber M, Wolfe SA, Maehr R. 2014.. Cas9 effector-mediated regulation of transcription and differentiation in human pluripotent stem cells. . Development 141::219–23
     [Crossref] [Google Scholar]
  58. Klann TS, Black JB, Chellappan M, Safi A, Song L, et al. 2017.. CRISPR-Cas9 epigenome editing enables high-throughput screening for functional regulatory elements in the human genome. . Nat. Biotechnol. 35::561–68
     [Crossref] [Google Scholar]
  59. Konermann S, Brigham MD, Trevino AE, Joung J, Abudayyeh OO, et al. 2015.. Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. . Nature 517::583–88
     [Crossref] [Google Scholar]
  60. Koonin EV, Makarova KS, Zhang F. 2017.. Diversity, classification and evolution of CRISPR-Cas systems. . Curr. Opin. Microbiol. 37::67–78
     [Crossref] [Google Scholar]
  61. Kumar P, Courtes M, Lemmers C, Le Digarcher A, Coku I, et al. 2023.. Functional mapping of microRNA promoters with dCas9 fused to transcriptional regulators. . Front. Genet. 14::1147222
     [Crossref] [Google Scholar]
  62. Kunii A, Hara Y, Takenaga M, Hattori N, Fukazawa T, et al. 2018.. Three-component repurposed technology for enhanced expression: highly accumulable transcriptional activators via branched tag arrays. . CRISPR J. 1::337–47
     [Crossref] [Google Scholar]
  63. Labun K, Montague TG, Gagnon JA, Thyme SB, Valen E. 2016.. CHOPCHOP v2: a web tool for the next generation of CRISPR genome engineering. . Nucleic Acids Res. 44::W272–76
     [Crossref] [Google Scholar]
  64. Labun K, Montague TG, Krause M, Torres Cleuren YN, Tjeldnes H, Valen E. 2019.. CHOPCHOP v3: expanding the CRISPR web toolbox beyond genome editing. . Nucleic Acids Res. 47::W171–74
     [Crossref] [Google Scholar]
  65. Law CT, Wei L, Tsang FH, Chan CY, Xu IM, et al. 2019.. HELLS regulates chromatin remodeling and epigenetic silencing of multiple tumor suppressor genes in human hepatocellular carcinoma. . Hepatology 69::2013–30
     [Crossref] [Google Scholar]
  66. Li G, Kryczek I, Nam J, Li X, Li S, et al. 2021.. LIMIT is an immunogenic lncRNA in cancer immunity and immunotherapy. . Nat. Cell Biol. 23::526–37
     [Crossref] [Google Scholar]
  67. Li Z, Zhang D, Xiong X, Yan B, Xie W, et al. 2017.. A potent Cas9-derived gene activator for plant and mammalian cells. . Nat. Plants 3::930–36
     [Crossref] [Google Scholar]
  68. Liao HK, Hatanaka F, Araoka T, Reddy P, Wu MZ, et al. 2017.. In vivo target gene activation via CRISPR/Cas9-mediated trans-epigenetic modulation. . Cell 171::1495–507.e15
     [Crossref] [Google Scholar]
  69. Lin S, Ewen-Campen B, Ni X, Housden BE, Perrimon N. 2015.. In vivo transcriptional activation using CRISPR/Cas9 in Drosophila. . Genetics 201::433–42
     [Crossref] [Google Scholar]
  70. Liu H, Wei Z, Dominguez A, Li Y, Wang X, Qi LS. 2015.. CRISPR-ERA: a comprehensive design tool for CRISPR-mediated gene editing, repression and activation. . Bioinformatics 31::3676–78
     [Crossref] [Google Scholar]
  71. Liu Q, Zhao K, Wang C, Zhang Z, Zheng C, et al. 2019.. Multistage delivery nanoparticle facilitates efficient CRISPR/dCas9 activation and tumor growth suppression in vivo. . Adv. Sci. 6::1801423
     [Crossref] [Google Scholar]
  72. Long L, Guo H, Yao D, Xiong K, Li Y, et al. 2015.. Regulation of transcriptionally active genes via the catalytically inactive Cas9 in C. elegans and D. rerio. . Cell Res. 25::638–41
     [Crossref] [Google Scholar]
  73. Maeder ML, Linder SJ, Cascio VM, Fu Y, Ho QH, Joung JK. 2013.. CRISPR RNA-guided activation of endogenous human genes. . Nat. Methods 10::977–79
     [Crossref] [Google Scholar]
  74. Mali P, Aach J, Stranges PB, Esvelt KM, Moosburner M, et al. 2013a.. CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. . Nat. Biotechnol. 31::833–38
     [Crossref] [Google Scholar]
  75. Mali P, Yang L, Esvelt KM, Aach J, Guell M, et al. 2013b.. RNA-guided human genome engineering via Cas9. . Science 339::823–26
     [Crossref] [Google Scholar]
  76. Marraffini LA, Sontheimer EJ. 2008.. CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA. . Science 322::1843–45
     [Crossref] [Google Scholar]
  77. Mikkelsen NS, Hernandez SS, Jensen TI, Schneller JL, Bak RO. 2023.. Enrichment of transgene integrations by transient CRISPR activation of a silent reporter gene. . Mol. Ther. Methods Clin. Dev. 29::1–16
     [Crossref] [Google Scholar]
  78. Mojica FJ, Díez-Villaseñor C, García-Martínez J, Soria E. 2005.. Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. . J. Mol. Evol. 60::174–82
     [Crossref] [Google Scholar]
  79. Mojica FJ, Díez-Villaseñor C, Soria E, Juez G. 2000.. Biological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria. . Mol. Microbiol. 36::244–46
     [Crossref] [Google Scholar]
  80. Mojica FJ, Juez G, Rodríguez-Valera F. 1993.. Transcription at different salinities of Haloferax mediterranei sequences adjacent to partially modified PstI sites. . Mol. Microbiol. 9::613–21
     [Crossref] [Google Scholar]
  81. Mojica FJM, Díez-Villaseñor C, García-Martínez J, Almendros C. 2009.. Short motif sequences determine the targets of the prokaryotic CRISPR defence system. . Microbiology 155::733–40
     [Crossref] [Google Scholar]
  82. Montague TG, Cruz JM, Gagnon JA, Church GM, Valen E. 2014.. CHOPCHOP: a CRISPR/Cas9 and TALEN web tool for genome editing. . Nucleic Acids Res. 42::W401–7
     [Crossref] [Google Scholar]
  83. Morita S, Horii T, Kimura M, Hatada I. 2020.. Synergistic upregulation of target genes by TET1 and VP64 in the dCas9-SunTag platform. . Int. J. Mol. Sci. 21::1574
     [Crossref] [Google Scholar]
  84. Müller N, Lorenz C, Ostendorp J, Heisel FS, Friese UP, et al. 2023.. Characterizing evolutionary dynamics reveals strategies to exhaust the spectrum of subclonal resistance in EGFR-mutant lung cancer. . Cancer Res. 83::2471–79
     [Crossref] [Google Scholar]
  85. Nayak S, Aich M, Kumar A, Sengupta S, Bajad P, et al. 2018.. Novel internal regulators and candidate miRNAs within miR-379/miR-656 miRNA cluster can alter cellular phenotype of human glioblastoma. . Sci. Rep. 8::7673
     [Crossref] [Google Scholar]
  86. Nihongaki Y, Kawano F, Nakajima T, Sato M. 2015.. Photoactivatable CRISPR-Cas9 for optogenetic genome editing. . Nat. Biotechnol. 33::755–60
     [Crossref] [Google Scholar]
  87. Peabody DS. 1993.. The RNA binding site of bacteriophage MS2 coat protein. . EMBO J. 12::595–600
     [Crossref] [Google Scholar]
  88. Perez-Pinera P, Kocak DD, Vockley CM, Adler AF, Kabadi AM, et al. 2013.. RNA-guided gene activation by CRISPR-Cas9-based transcription factors. . Nat. Methods 10::973–76
     [Crossref] [Google Scholar]
  89. Platt RJ, Chen S, Zhou Y, Yim MJ, Swiech L, et al. 2014.. CRISPR-Cas9 knockin mice for genome editing and cancer modeling. . Cell 159::440–55
     [Crossref] [Google Scholar]
  90. Polstein LR, Gersbach CA. 2015.. A light-inducible CRISPR-Cas9 system for control of endogenous gene activation. . Nat. Chem. Biol. 11::198–200
     [Crossref] [Google Scholar]
  91. Pourcel C, Salvignol G, Vergnaud G. 2005.. CRISPR elements in Yersinia pestis acquire new repeats by preferential uptake of bacteriophage DNA, and provide additional tools for evolutionary studies. . Microbiology 151::653–63
     [Crossref] [Google Scholar]
  92. Qi LS, Larson MH, Gilbert LA, Doudna JA, Weissman JS, et al. 2013.. Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. . Cell 152::1173–83
     [Crossref] [Google Scholar]
  93. Quinn JJ, Chang HY. 2016.. Unique features of long non-coding RNA biogenesis and function. . Nat. Rev. Genet. 17::47–62
     [Crossref] [Google Scholar]
  94. Rocha CRR, Reily Rocha A, Molina Silva M, Rodrigues Gomes L, Teatin Latancia M, et al. 2020.. Revealing temozolomide resistance mechanisms via genome-wide CRISPR libraries. . Cells 9::2573
     [Crossref] [Google Scholar]
  95. Ruben SM, Narayanan R, Klement JF, Chen CH, Rosen CA. 1992.. Functional characterization of the NF-κB p65 transcriptional activator and an alternatively spliced derivative. . Mol. Cell. Biol. 12::444–54
     [Google Scholar]
  96. Sanson KR, Hanna RE, Hegde M, Donovan KF, Strand C, et al. 2018.. Optimized libraries for CRISPR-Cas9 genetic screens with multiple modalities. . Nat. Commun. 9::5416
     [Crossref] [Google Scholar]
  97. Sapranauskas R, Gasiunas G, Fremaux C, Barrangou R, Horvath P, Siksnys V. 2011.. The Streptococcus thermophilus CRISPR/Cas system provides immunity in Escherichia coli. . Nucleic Acids Res. 39::9275–82
     [Crossref] [Google Scholar]
  98. Saratov V, Ngo QA, Pedot G, Sidorov S, Wachtel M, et al. 2022.. CRISPR activation screen identifies TGFβ-associated PEG10 as a crucial tumor suppressor in Ewing sarcoma. . Sci. Rep. 12::10671
     [Crossref] [Google Scholar]
  99. Schmitz ML, Baeuerle PA. 1991.. The p65 subunit is responsible for the strong transcription activating potential of NF-κB. . EMBO J. 10::3805–17
     [Crossref] [Google Scholar]
  100. Seipel K, Georgiev O, Schaffner W. 1992.. Different activation domains stimulate transcription from remote (‘enhancer’) and proximal (‘promoter’) positions. . EMBO J. 11::4961–68
     [Crossref] [Google Scholar]
  101. Sgro A, Cursons J, Waryah C, Woodward EA, Foroutan M, et al. 2023.. Epigenetic reactivation of tumor suppressor genes with CRISPRa technologies as precision therapy for hepatocellular carcinoma. . Clin. Epigenetics 15::73
     [Crossref] [Google Scholar]
  102. Shamloo S, Kloetgen A, Petroulia S, Hockemeyer K, Sievers S, et al. 2023.. Integrative CRISPR activation and small molecule inhibitor screening for lncRNA mediating BRAF inhibitor resistance in melanoma. . Biomedicines 11::2054
     [Crossref] [Google Scholar]
  103. Shen Y, Eng JS, Fajardo F, Liang L, Li C, et al. 2022.. Cancer cell-intrinsic resistance to BiTE therapy is mediated by loss of CD58 costimulation and modulation of the extrinsic apoptotic pathway. . J. Immunother. Cancer 10::e004348
     [Crossref] [Google Scholar]
  104. Shi Y, Kroeger PE, Morimoto RI. 1995.. The carboxyl-terminal transactivation domain of heat shock factor 1 is negatively regulated and stress responsive. . Mol. Cell. Biol. 15::4309–18
     [Crossref] [Google Scholar]
  105. Sui A, Xu Y, Yang J, Pan B, Wu J, et al. 2019.. The histone H3 Lys 27 demethylase KDM6B promotes migration and invasion of glioma cells partly by regulating the expression of SNAI1. . Neurochem. Int. 124::123–29
     [Crossref] [Google Scholar]
  106. Tak YE, Kleinstiver BP, Nuñez JK, Hsu JY, Horng JE, et al. 2017.. Inducible and multiplex gene regulation using CRISPR-Cpf1-based transcription factors. . Nat. Methods 14::1163–66
     [Crossref] [Google Scholar]
  107. Takayama K, Mizuguchi H. 2018.. Generation of optogenetically modified adenovirus vector for spatiotemporally controllable gene therapy. . ACS Chem. Biol. 13::449–54
     [Crossref] [Google Scholar]
  108. Tanenbaum ME, Gilbert LA, Qi LS, Weissman JS, Vale RD. 2014.. A protein-tagging system for signal amplification in gene expression and fluorescence imaging. . Cell 159::635–46
     [Crossref] [Google Scholar]
  109. Thege FI, Rupani DN, Barathi BB, Manning SL, Maitra A, et al. 2022.. A programmable in vivo CRISPR activation model elucidates the oncogenic and immunosuppressive functions of MYC in lung adenocarcinoma. . Cancer Res. 82::2761–76
     [Crossref] [Google Scholar]
  110. Tong B, Sun Y. 2023.. Activation of young LINE-1 elements by CRISPRa. . Int. J. Mol. Sci. 25::424
     [Crossref] [Google Scholar]
  111. Wang C, Li D, Zhang L, Jiang S, Liang J, et al. 2019.. RNA sequencing analyses of gene expression during Epstein-Barr virus infection of primary B lymphocytes. . J. Virol. 93::e00226-19
     [Google Scholar]
  112. Wang D, Tai PWL, Gao G. 2019.. Adeno-associated virus vector as a platform for gene therapy delivery. . Nat. Rev. Drug Discov. 18::358–78
     [Crossref] [Google Scholar]
  113. Wang G, Chow RD, Bai Z, Zhu L, Errami Y, et al. 2019.. Multiplexed activation of endogenous genes by CRISPRa elicits potent antitumor immunity. . Nat. Immunol. 20::1494–505
     [Crossref] [Google Scholar]
  114. Wang W, Song F, Feng X, Chu X, Dai H, et al. 2021.. Functional interrogation of enhancer connectome prioritizes candidate target genes at ovarian cancer susceptibility loci. . Front. Genet. 12::646179
     [Crossref] [Google Scholar]
  115. Wang Y, Zhao Y, Guo W, Yadav GS, Bhaskarla C, et al. 2022.. Genome-wide gain-of-function screening characterized lncRNA regulators for tumor immune response. . Sci. Adv. 8::eadd0005
     [Crossref] [Google Scholar]
  116. Wangensteen KJ, Wang YJ, Dou Z, Wang AW, Mosleh-Shirazi E, et al. 2018.. Combinatorial genetics in liver repopulation and carcinogenesis with a in vivo CRISPR activation platform. . Hepatology 68::663–76
     [Crossref] [Google Scholar]
  117. Wold WS, Toth K. 2013.. Adenovirus vectors for gene therapy, vaccination and cancer gene therapy. . Curr. Gene Ther. 13::421–33
     [Crossref] [Google Scholar]
  118. Yang Y, Feng Q, Hu K, Cheng F. 2021.. Using CRISPRa and CRISPRi technologies to study the biological functions of ITGB5, TIMP1, and TMEM176B in prostate cancer cells. . Front. Mol. Biosci. 8::676021
     [Crossref] [Google Scholar]
  119. Yang Z, Pietrobon V, Bobbin M, Stefanson O, Yang J, et al. 2023.. Nanoscale, antigen encounter-dependent, IL-12 delivery by CAR T cells plus PD-L1 blockade for cancer treatment. . J. Transl. Med. 21::158
     [Crossref] [Google Scholar]
  120. Young JK, Gasior SL, Jones S, Wang L, Navarro P, et al. 2019.. The repurposing of type I-E CRISPR-Cascade for gene activation in plants. . Commun. Biol. 2::383
     [Crossref] [Google Scholar]
  121. Zalatan JG, Lee ME, Almeida R, Gilbert LA, Whitehead EH, et al. 2015.. Engineering complex synthetic transcriptional programs with CRISPR RNA scaffolds. . Cell 160::339–50
     [Crossref] [Google Scholar]
  122. Zetsche B, Gootenberg JS, Abudayyeh OO, Slaymaker IM, Makarova KS, et al. 2015.. Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. . Cell 163::759–71
     [Crossref] [Google Scholar]
  123. Zhang B, Ren Z, Zheng H, Lin M, Chen G, et al. 2023.. CRISPR activation screening in a mouse model for drivers of hepatocellular carcinoma growth and metastasis. . iScience 26::106099
     [Crossref] [Google Scholar]
  124. Zhang X, Wang J, Cheng Q, Zheng X, Zhao G, Wang J. 2017.. Multiplex gene regulation by CRISPR-ddCpf1. . Cell Discov. 3::17018
     [Crossref] [Google Scholar]
  125. Zhang X, Wang W, Shan L, Han L, Ma S, et al. 2018a.. Gene activation in human cells using CRISPR/Cpf1-p300 and CRISPR/Cpf1-SunTag systems. . Protein Cell 9::380–83
     [Crossref] [Google Scholar]
  126. Zhang X, Xu L, Fan R, Gao Q, Song Y, et al. 2018b.. Genetic editing and interrogation with Cpf1 and caged truncated pre-tRNA-like crRNA in mammalian cells. . Cell Discov. 4::36
     [Crossref] [Google Scholar]
  127. Zhao WS, Yan WP, Chen DB, Dai L, Yang YB, et al. 2019.. Genome-scale CRISPR activation screening identifies a role of ELAVL2-CDKN1A axis in paclitaxel resistance in esophageal squamous cell carcinoma. . Am. J. Cancer Res. 9::1183–200
     [Google Scholar]
  128. Zheng B, Chen Y, Niu L, Zhang X, Yang Y, et al. 2024.. Modulating the tumoral SPARC content to enhance albumin-based drug delivery for cancer therapy. . J. Control. Release 366::596–610
     [Crossref] [Google Scholar]
  129. Zhou H, Liu J, Zhou C, Gao N, Rao Z, et al. 2018.. In vivo simultaneous transcriptional activation of multiple genes in the brain using CRISPR-dCas9-activator transgenic mice. . Nat. Neurosci. 21::440–46
     [Crossref] [Google Scholar]
  130. Zhu GD, Yu J, Sun ZY, Chen Y, Zheng HM, et al. 2021.. Genome-wide CRISPR/Cas9 screening identifies CARHSP1 responsible for radiation resistance in glioblastoma. . Cell Death. Dis. 12::724
     [Crossref] [Google Scholar]
  131. Zuo T, Wang L, Morrison C, Chang X, Zhang H, et al. 2007.. FOXP3 is an X-linked breast cancer suppressor gene and an important repressor of the HER-2/ErbB2 oncogene. . Cell 129::1275–86
     [Crossref] [Google Scholar]
/content/journals/10.1146/annurev-cancerbio-062624-104149
Loading
Awakening the Genome: CRISPR Activation to Unravel the Origin and Vulnerabilities of Cancer
Annual Review of Cancer Biology 9, 141 (2025); https://doi.org/10.1146/annurev-cancerbio-062624-104149
/content/journals/10.1146/annurev-cancerbio-062624-104149
/content/journals/10.1146/annurev-cancerbio-062624-104149
Loading

Data & Media loading...

Supplemental Materials

  • Supplemental Table 1

file format pdf download PDF

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error