Skip to main content
SpringerLink
Log in

Editing Cultured Human Cells: From Cell Lines to iPS Cells

  • Chapter
  • First Online:
Book cover Targeted Genome Editing Using Site-Specific Nucleases

Abstract

The human genome is complex, and the functions of many genes and specific genomic elements have not been fully explored. Cultured human cells, from conventional cell lines to iPS cells, are valuable tools that are used to study human genomics in the laboratory; however, the gene targeting efficiencies have generally been low in most of these human cells, making it difficult to assess the functions of these genes. The development of custom-engineered nucleases highlights the possibility of using different approaches to pursue functional genomic studies in cultured human cells. In this chapter, we review the chronological advances made in ZFNs, TALENs and CRISPR/Cas9 systems for gene disruption, locus-specific integration and gene correction. In addition, we summarize the emerging applications of tailor-made DNA binding modules for controlling the transcriptional state, modifying epigenetic marks and for live-cell imaging. The remaining challenges associated with increasing the target specificity, delivery and safety are also discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Bacman SR, Williams SL, Pinto M, Peralta S, Moraes CT (2013) Specific elimination of mutant mitochondrial genomes in patient-derived cells by mitoTALENs. Nat Med 19:1111–1113

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bae KH, Kwon YD, Shin HC, Hwang MS, Ryu EH, Park KS, Yang HY, Lee DK, Lee Y, Park J, Kwon HS, Kim HW, Yeh BI, Lee HW, Sohn SH, Yoon J, Seol W, Kim JS (2003) Human zinc fingers as building blocks in the construction of artificial transcription factors. Nat Biotechnol 21:275–280

    CAS  PubMed  Google Scholar 

  • Bhatia S, Pilquil C, Roth-Albin I, Draper JS (2013) Demarcation of stable subpopulations within the pluripotent hESC compartment. PLoS One 8:e57276

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bibikova M, Golic M, Golic KG, Carroll D (2002) Targeted chromosomal cleavage and mutagenesis in Drosophila using zinc-finger nucleases. Genetics 161:1169–1175

    CAS  PubMed Central  PubMed  Google Scholar 

  • Blancafort P, Segal DJ, Barbas CF 3rd (2004) Designing transcription factor architectures for drug discovery. Mol Pharmacol 66:1361–1371

    CAS  PubMed  Google Scholar 

  • Boch J, Scholze H, Schornack S, Landgraf A, Hahn S, Kay S, Lahaye T, Nickstadt A, Bonas U (2009) Breaking the code of DNA binding specificity of TAL-type III effectors. Science 326:1509–1512

    CAS  PubMed  Google Scholar 

  • Boissel S, Jarjour J, Astrakhan A, Adey A, Gouble A, Duchateau P, Shendure J, Stoddard B, Certo M, Baker D, Scharenberg A (2013) MegaTALs: a rare-cleaving nuclease architecture for therapeutic genome engineering. Nucleic Acids Res 42:2591–2601

    PubMed Central  PubMed  Google Scholar 

  • Buerstedde JM, Takeda S (1991) Increased ratio of targeted to random integration after transfection of chicken B cell lines. Cell 67:179–188

    CAS  PubMed  Google Scholar 

  • Capecchi MR (2001) Generating mice with targeted mutations. Nat Med 7:1086–1090

    CAS  PubMed  Google Scholar 

  • Cermak T, Doyle EL, Christian M, Wang L, Zhang Y, Schmidt C, Baller JA, Somia NV, Bogdanove AJ, Voytas DF (2011) Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting. Nucleic Acids Res 39:e82

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chames P, Epinat J-C, Guillier S, Patin A, Lacroix E, Pâques F (2005) In vivo selection of engineered homing endonucleases using double-strand break induced homologous recombination. Nucleic Acids Res 33:e178

    PubMed Central  PubMed  Google Scholar 

  • Chang C-J, Bouhassira EE (2012) Zinc-finger nuclease-mediated correction of α-thalassemia in iPS cells. Blood 120:3906–3914

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chapdelaine P, Pichavant C, Rousseau J, Pâques F, Tremblay JP (2010) Meganucleases can restore the reading frame of a mutated dystrophin. Gene Ther 17:846–858

    CAS  PubMed  Google Scholar 

  • Chen B, Gilbert LA, Cimini BA, Schnitzbauer J, Zhang W, Li G-W, Park J, Blackburn EH, Weissman JS, Qi LS, Huang B (2013) Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system. Cell 155:1479–1491

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cheng AW, Wang H, Yang H, Shi L, Katz Y, Theunissen TW, Rangarajan S, Shivalila CS, Dadon DB, Jaenisch R (2013) Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system. Cell Res 23:1163–1171

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chevalier BS, Monnat RJ Jr, Stoddard BL (2001) The homing endonuclease I-CreI uses three metals, one of which is shared between the two active sites. Nat Struct Biol 8:312–316

    CAS  PubMed  Google Scholar 

  • Cho S-W, Kim S, Kim JM, Kim J-S (2013) Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease. Nat Biotechnol 31:230–232

    CAS  PubMed  Google Scholar 

  • Choi S, Kim Y, Shim J, Park J, Wang R, Leach S, Liu J, Deng C, Ye Z, Jang Y (2013) Efficient drug screening and gene correction for treating liver disease using patient-specific stem cells. Hepatology 57:2458–2468

    CAS  PubMed Central  PubMed  Google Scholar 

  • Choulika A, Perrin A, Dujon B, Nicolas JF (1995) Induction of homologous recombination in mammalian chromosomes by using the I-SceI system of saccharomyces cerevisiae. Mol Cell Biol 15:1968–1973

    CAS  PubMed Central  PubMed  Google Scholar 

  • Christian M, Cermak T, Doyle EL, Schmidt C, Zhang F, Hummel A, Bogdanove AJ, Voytas DF (2010) Targeting DNA double-strand breaks with TAL effector nucleases. Genetics 186:757–761

    CAS  PubMed Central  PubMed  Google Scholar 

  • Coluccio A, Miselli F, Lombardo A, Marconi A, Malagoli Tagliazucchi G, Gonçalves MA, Pincelli C, Maruggi G, Del Rio M, Naldini L, Larcher F, Mavilio F, Recchia A (2013) Targeted gene addition in human epithelial stem cells by zinc-finger nuclease-mediated homologous recombination. Mol ther 21:1695–1704

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Marraffini LA, Zhang F (2013) Multiplex genome engineering using CRISPR/Cas systems. Science 339:819–823

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cornu TI, Thibodeau-Beganny S, Guhl E, Alwin S, Eichtinger M, Joung JK, Joung JK, Cathomen T (2008) DNA-binding specificity is a major determinant of the activity and toxicity of zinc-finger nucleases. Mol Ther 16:352–358

    CAS  PubMed  Google Scholar 

  • Cradick TJ, Fine EJ, Antico CJ, Bao G (2013) CRISPR/Cas9 systems targeting β-globin and CCR5 genes have substantial off-target activity. Nucleic Acids Res 41:9584–9592

    CAS  PubMed Central  PubMed  Google Scholar 

  • Davis RP, Ng ES, Costa M, Mossman AK, Sourris K, Elefanty AG, Stanley EG (2008) Targeting a GFP reporter gene to the MIXL1 locus of human embryonic stem cells identifies human primitive streak-like cells and enables isolation of primitive hematopoietic precursors. Blood 111:1876–1884

    CAS  PubMed  Google Scholar 

  • DeKelver R, Choi V, Moehle E, Paschon D, Hockemeyer D, Meijsing S, Sancak Y, Cui X, Steine E, Miller J, Tam P, Bartsevich V, Meng X, Rupniewski I, Gopalan S, Sun H, Pitz K, Rock J, Zhang L, Davis G, Rebar E, Cheeseman I, Yamamoto K, Sabatini D, Jaenisch R, Gregory P, Urnov F (2010) Functional genomics, proteomics, and regulatory DNA analysis in isogenic settings using zinc finger nuclease-driven transgenesis into a safe harbor locus in the human genome. Genome Res 20:1133–1142

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ding Q, Lee Y-K, Schaefer EAK, Peters DT, Veres A, Kim K, Kuperwasser N, Motola DL, Meissner TB, Hendriks WT, Trevisan M, Gupta RM, Moisan A, Banks E, Friesen M, Schinzel RT, Xia F, Tang A, Xia Y, Figueroa E, Wann A, Ahfeldt T, Daheron L, Zhang F, Rubin LL, Peng LF, Chung RT, Musunuru K, Cowan CA (2013a) A TALEN genome-editing system for generating human stem cell-based disease models. Cell Stem Cell 12:238–251

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ding Q, Regan SN, Xia Y, Oostrom LA, Cowan CA, Musunuru K (2013b) Enhanced efficiency of human pluripotent stem cell genome editing through replacing TALENs with CRISPRs. Cell Stem Cell 12:393–394

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dreier B, Segal DJ, Barbas CF 3rd (2000) Insights into the molecular recognition of the 5′-GNN-3′ family of DNA sequences by zinc finger domains. J Mol Biol 303:489–502

    CAS  PubMed  Google Scholar 

  • Dreier B, Beerli RR, Segal DJ, Flippin JD, Barbas CF 3rd (2001) Development of zinc finger domains for recognition of the 5′-ANN-3′ family of DNA sequences and their use in the construction of artificial transcription factors. J Biol Chem 276:29466–29478

    CAS  PubMed  Google Scholar 

  • Ebina H, Misawa N, Kanemura Y, Koyanagi Y (2013) Harnessing the CRISPR/Cas9 system to disrupt latent HIV-1 provirus. Sci Rep 3:2510

    PubMed Central  PubMed  Google Scholar 

  • Epinat J-C, Arnould S, Chames P, Rochaix P, Desfontaines D, Puzin C, Patin A, Zanghellini A, Pâques F, Lacroix E (2003) A novel engineered meganuclease induces homologous recombination in yeast and mammalian cells. Nucleic Acids Res 31:2952–2962

    CAS  PubMed Central  PubMed  Google Scholar 

  • Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156

    CAS  PubMed  Google Scholar 

  • Folger KR, Wong EA, Wahl G, Capecchi MR (1982) Patterns of integration of DNA microinjected into cultured mammalian cells: evidence for homologous recombination between injected plasmid DNA molecules. Mol Cell Biol 2:1372–1387

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fu Y, Sander JD, Reyon D, Cascio VM, Joung JK (2014) Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nat Biotechnol 32:279–284

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fujita T, Fujii H (2013) Efficient isolation of specific genomic regions and identification of associated proteins by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) using CRISPR. Biochem Biophys Res Commun 439:132–136

    CAS  PubMed  Google Scholar 

  • Fujita T, Asano Y, Ohtsuka J, Takada Y, Saito K, Ohki R, Fujii H (2013) Identification of telomere-associated molecules by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP). Sci Rep 3:3171

    PubMed Central  PubMed  Google Scholar 

  • Garçon L, Ge J, Manjunath SH, Mills JA, Apicella M, Parikh S, Sullivan LM, Podsakoff GM, Gadue P, French DL, Mason PJ, Bessler M, Weiss MJ (2013) Ribosomal and hematopoietic defects in induced pluripotent stem cells derived from diamond Blackfan anemia patients. Blood 122:912–921

    PubMed Central  PubMed  Google Scholar 

  • Genovese P, Schiroli G, Escobar G, Di Tomaso T, Firrito C, Calabria A, Moi D, Mazzieri R, Bonini C, Holmes MC, Gregory PD, van der Burg M, Gentner B, Montini E, Lombardo A, Naldini L (2014) Targeted genome editing in human repopulating haematopoietic stem cells. Nature 510:235–240

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gilbert LA, Larson MH, Morsut L, Liu Z, Brar GA, Torres SE, Stern-Ginossar N, Brandman O, Whitehead EH, Doudna JA, Lim WA, Weissman JS, Qi LS (2013) CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 154:442–451

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gonzalez F, Zhu Z, Shi ZD, Lelli K, Verma N, Li QV, Huangfu D (2014) An iCRISPR platform for rapid, multiplexable, and inducible genome editing in human pluripotent stem cells. Cell Stem Cell 15:1–12

    Google Scholar 

  • Grizot S, Smith J, Daboussi F, Prieto J, Redondo P, Merino N, Villate M, Thomas S, Lemaire L, Montoya G, Blanco FJ, Pâques F, Duchateau P (2009) Efficient targeting of a SCID gene by an engineered single-chain homing endonuclease. Nucleic Acids Res 37

    Google Scholar 

  • Grizot S, Epinat J-C, Thomas S, Duclert A, Rolland S, Pâques F, Duchateau P (2010) Generation of redesigned homing endonucleases comprising DNA-binding domains derived from two different scaffolds. Nucleic Acids Res 38:2006–2018

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hockemeyer D, Soldner F, Beard C, Gao Q, Mitalipova M, DeKelver RC, Katibah GE, Amora R, Boydston EA, Zeitler B, Meng X, Miller JC, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Jaenisch R (2009) Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases. Nat Biotechnol 27:851–857

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hockemeyer D, Wang H, Kiani S, Lai CS, Gao Q, Cassady JP, Cost GJ, Zhang L, Santiago Y, Miller JC, Zeitler B, Cherone JM, Meng X, Hinkley SJ, Rebar EJ, Gregory PD, Urnov FD, Jaenisch R (2011) Genetic engineering of human pluripotent cells using TALE nucleases. Nat Biotechnol 29:731–734

    CAS  PubMed Central  PubMed  Google Scholar 

  • Holkers M, Maggio I, Liu J, Janssen JM, Miselli F, Mussolino C, Recchia A, Cathomen T, Gonçalves MAFV (2013) Differential integrity of TALE nuclease genes following adenoviral and lentiviral vector gene transfer into human cells. Nucleic Acids Res 41:e63

    CAS  PubMed Central  PubMed  Google Scholar 

  • Holt N, Wang J, Kim K, Friedman G, Wang X, Taupin V, Crooks GM, Kohn DB, Gregory PD, Holmes MC, Cannon PM (2010) Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo. Nat Biotechnol 28:839–847

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hotta A, Cheung AY, Farra N, Vijayaragavan K, Seguin CA, Draper JS, Pasceri P, Maksakova IA, Mager DL, Rossant J, Bhatia M, Ellis J (2009) Isolation of human iPS cells using EOS lentiviral vectors to select for pluripotency. Nat Methods 6:370–376

    CAS  PubMed  Google Scholar 

  • Hsu PD, Scott DA, Weinstein JA, Ran FA, Konermann S, Agarwala V, Li Y, Fine EJ, Wu X, Shalem O, Cradick TJ, Marraffini LA, Bao G, Zhang F (2013) DNA targeting specificity of RNA-guided Cas9 nucleases. Nat Biotechnol 31:827–832

    CAS  PubMed Central  PubMed  Google Scholar 

  • Isalan M, Klug A, Choo Y (1998) Comprehensive DNA recognition through concerted interactions from adjacent zinc fingers. Biochemistry 37:12026–12033

    CAS  PubMed  Google Scholar 

  • Jaenisch R (1977) Germ line integration of moloney leukemia virus: effect of homozygosity at the m-mulV locus. Cell 12:691–696

    CAS  PubMed  Google Scholar 

  • Jia J, Jin Y, Bian T, Wu D, Yang L, Terada N, Wu W, Jin S (2014) Bacterial delivery of TALEN proteins for human genome editing. PLoS One 9:e91547

    PubMed Central  PubMed  Google Scholar 

  • Jiang J, Jing Y, Cost G, Chiang J, Kolpa H, Cotton A, Carone D, Carone B, Shivak D, Guschin D, Pearl J, Rebar E, Byron M, Gregory P, Brown C, Urnov F, Hall L, Lawrence J (2013a) Translating dosage compensation to trisomy 21. Nature 500:296–300

    CAS  PubMed  Google Scholar 

  • Jiang W, Bikard D, Cox D, Zhang F, Marraffini LA (2013b) RNA-guided editing of bacterial genomes using CRISPR-Cas systems. Nat Biotechnol 31:233–239

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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 337:816–821

    CAS  PubMed  Google Scholar 

  • Jinek M, East A, Cheng A, Lin S, Ma E, Doudna J (2013) RNA-programmed genome editing in human cells. Elife 2:e00471

    PubMed Central  PubMed  Google Scholar 

  • Kim JA, Cho K, Shin MS, Lee WG, Jung N, Chung C, Chang JK (2008) A novel electroporation method using a capillary and wire-type electrode. Biosens Bioelectron 23:1353–1360

    CAS  PubMed  Google Scholar 

  • Kim HJ, Lee HJ, Kim H, Cho SW, Kim JS (2009) Targeted genome editing in human cells with zinc finger nucleases constructed via modular assembly. Genome Res 19:1279–1288

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kim Y, Kweon J, Kim A, Chon JK, Yoo JY, Kim HJ, Kim S, Lee C, Jeong E, Chung E, Kim D, Lee MS, Go EM, Song HJ, Kim H, Cho N, Bang D, Kim S, Kim J-S (2013a) A library of TAL effector nucleases spanning the human genome. Nat Biotechnol 31:251–258

    CAS  PubMed  Google Scholar 

  • Kim Y-K, Wee G, Park J, Kim J, Baek D, Kim J-S, Kim VN (2013b) TALEN-based knockout library for human microRNAs. Nat Struct Mol Biol 20:1458–1464

    CAS  PubMed  Google Scholar 

  • Kim S, Kim D, Cho S-W, Kim J, Kim J-S (2014) Highly efficient RNA-guided genome editing in human cells via delivery of purified Cas9 ribonucleoproteins. Genome Res 24:1012–1019

    CAS  PubMed Central  PubMed  Google Scholar 

  • Koike-Yusa H, Li Y, Tan E-P, Velasco-Herrera MDC, Yusa K (2014) Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library. Nat Biotechnol 32:267–273

    CAS  PubMed  Google Scholar 

  • Konermann S, Brigham MD, Trevino AE, Hsu PD, Heidenreich M, Cong L, Platt RJ, Scott DA, Church GM, Zhang F (2013) Optical control of mammalian endogenous transcription and epigenetic states. Nature 500:472–476

    CAS  PubMed  Google Scholar 

  • Lee HJ, Kweon J, Kim E, Kim S, Kim J-S (2012) Targeted chromosomal duplications and inversions in the human genome using zinc finger nucleases. Genome Res 22:539–548

    CAS  PubMed Central  PubMed  Google Scholar 

  • Li H, Haurigot V, Doyon Y, Li T, Wong SY, Bhagwat AS, Malani N, Anguela XM, Sharma R, Ivanciu L, Murphy SL, Finn JD, Khazi FR, Zhou S, Paschon DE, Rebar EJ, Bushman FD, Gregory PD, Holmes MC, High KA (2011) In vivo genome editing restores haemostasis in a mouse model of haemophilia. Nature 475:217–221

    CAS  PubMed Central  PubMed  Google Scholar 

  • Li S-J, Shi R-Z, Bai Y-P, Hong D, Yang W, Wang X, Mo L, Zhang G-G (2013) Targeted introduction of tissue plasminogen activator (TPA) at the AAVS1 locus in mesenchymal stem cells (MSCs) and its stable and effective expression. Biochem Biophys Res Commun 437:74–78

    CAS  PubMed  Google Scholar 

  • Lin Y, Cradick TJ, Brown MT, Deshmukh H, Ranjan P, Sarode N, Wile BM, Vertino PM, Stewart FJ, Bao G (2014) CRISPR/Cas9 systems have off-target activity with insertions or deletions between target DNA and guide RNA sequences. Nucleic Acids Res 42:7473–7485

    Google Scholar 

  • Lisa Li H, Nakano T, Hotta A (2014) Genetic correction using engineered nucleases for gene therapy applications. Dev Growth Differ 56:63–77

    CAS  Google Scholar 

  • Lombardo A, Genovese P, Beausejour CM, Colleoni S, Lee Y-L, Kim KA, Ando D, Urnov FD, Galli C, Gregory PD, Holmes MC, Naldini L (2007) Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery. Nat Biotechnol 25:1298–1306

    CAS  PubMed  Google Scholar 

  • Lombardo A, Cesana D, Genovese P, Di Stefano B, Provasi E, Colombo DF, Neri M, Magnani Z, Cantore A, Lo Riso P, Damo M, Pello OM, Holmes MC, Gregory PD, Gritti A, Broccoli V, Bonini C, Naldini L (2011) Site-specific integration and tailoring of cassette design for sustainable gene transfer. Nat Methods 8:861–869

    CAS  PubMed  Google Scholar 

  • Ma H, Reyes-Gutierrez P, Pederson T (2013) Visualization of repetitive DNA sequences in human chromosomes with transcription activator-like effectors. Proc Natl Acad Sci U S A 110:21048–21053

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ma N, Liao B, Zhang H, Wang L, Shan Y, Xue Y, Huang K, Chen S, Zhou X, Chen Y, Pei D, Pan G (2014) Transcription activator-like effector nuclease (TALEN)-mediated gene correction in integration-free β-thalassemia induced pluripotent stem cells. J Biol Chem 288:34671–34679

    Google Scholar 

  • Mae S, Shono A, Shiota F, Yasuno T, Kajiwara M, Gotoda-Nishimura N, Arai S, Sato-Otubo A, Toyoda T, Takahashi K, Nakayama N, Cowan CA, Aoi T, Ogawa S, McMahon AP, Yamanaka S, Osafune K (2013) Monitoring and robust induction of nephrogenic intermediate mesoderm from human pluripotent stem cells. Nat Commun 4:1367

    PubMed  Google Scholar 

  • Maeder ML, Thibodeau-Beganny S, Osiak A, Wright DA, Anthony RM, Eichtinger M, Jiang T, Foley JE, Winfrey RJ, Townsend JA, Unger-Wallace E, Sander JD, Muller-Lerch F, Fu F, Pearlberg J, Gobel C, Dassie JP, Pruett-Miller SM, Porteus MH, Sgroi DC, Iafrate AJ, Dobbs D, McCray PB Jr, Cathomen T, Voytas DF, Joung JK (2008) Rapid "open-source" engineering of customized zinc-finger nucleases for highly efficient gene modification. Mol Cell 31:294–301

    CAS  PubMed Central  PubMed  Google Scholar 

  • Maeder ML, Linder SJ, Cascio VM, Fu Y, Ho QH, Joung JK (2013a) CRISPR RNA-guided activation of endogenous human genes. Nat Methods 10:977–979

    CAS  PubMed Central  PubMed  Google Scholar 

  • Maeder ML, Linder SJ, Reyon D, Angstman JF, Fu Y, Sander JD, Joung JK (2013b) Robust, synergistic regulation of human gene expression using TALE activators. Nat Methods 10(3):243–245

    CAS  PubMed Central  PubMed  Google Scholar 

  • Maggio I, Holkers M, Liu J, Janssen JM, Chen X, Gonçalves MAFV (2014) Adenoviral vector delivery of RNA-guided CRISPR/Cas9 nuclease complexes induces targeted mutagenesis in a diverse array of human cells. Sci Rep 4:5105

    PubMed Central  PubMed  Google Scholar 

  • Maier DA, Brennan AL, Jiang S, Binder-Scholl GK, Lee G, Plesa G, Zheng Z, Cotte J, Carpenito C, Wood T, Spratt SK, Ando D, Gregory P, Holmes MC, Perez EE, Riley JL, Carroll RG, June CH, Levine BL (2013) Efficient clinical scale gene modification via zinc finger nuclease-targeted disruption of the HIV co-receptor CCR5. Hum Gene Ther 24:245–258

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mali P, Aach J, Stranges PB, Esvelt KM, Moosburner M, Kosuri S, Yang L, Church GM (2013a) CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. Nat Biotechnol 31:833–838

    CAS  PubMed  Google Scholar 

  • Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, Norville JE, Church GM (2013b) RNA-guided human genome engineering via Cas9. Science 339:823–826

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mendenhall EM, Williamson KE, Reyon D, Zou JY, Ram O, Joung JK, Bernstein BE (2013) Locus-specific editing of histone modifications at endogenous enhancers. Nat Biotechnol 31:1133–1136

    CAS  PubMed  Google Scholar 

  • Miller JC, Tan S, Qiao G, Barlow KA, Wang J, Xia DF, Meng X, Paschon DE, Leung E, Hinkley SJ, Dulay GP, Hua KL, Ankoudinova I, Cost GJ, Urnov FD, Zhang HS, Holmes MC, Zhang L, Gregory PD, Rebar EJ (2011) A TALE nuclease architecture for efficient genome editing. Nat Biotechnol 29:143–148

    CAS  PubMed  Google Scholar 

  • Miyanari Y, Ziegler-Birling C, Torres-Padilla ME (2013) Live visualization of chromatin dynamics with fluorescent TALEs. Nat Struct Mol Biol 20:1321–1324

    CAS  PubMed  Google Scholar 

  • Moscou MJ, Bogdanove AJ (2009) A simple cipher governs DNA recognition by TAL effectors. Science 326:1501

    CAS  PubMed  Google Scholar 

  • Mussolino C, Morbitzer R, Lütge F, Dannemann N, Lahaye T, Cathomen T (2011) A novel TALE nuclease scaffold enables high genome editing activity in combination with low toxicity. Nucleic Acids Res 39:9283–9293

    CAS  PubMed Central  PubMed  Google Scholar 

  • Neumann E, Schaefer-Ridder M, Wang Y, Hofschneider PH (1982) Gene transfer into mouse lyoma cells by electroporation in high electric fields. EMBO J 1:841–845

    CAS  PubMed Central  PubMed  Google Scholar 

  • Osborn MJ, Starker CG, McElroy AN, Webber BR, Riddle MJ, Xia L, DeFeo AP, Gabriel R, Schmidt M, von Kalle C, Carlson DF, Maeder ML, Joung JK, Wagner JE, Voytas DF, Blazar BR, Tolar J (2013) TALEN-based gene correction for epidermolysis bullosa. Mol Ther 21:1151–1159

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ousterout DG, Perez-Pinera P, Thakore PI, Kabadi AM, Brown MT, Qin X, Fedrigo O, Mouly V, Tremblay JP, Gersbach CA (2013) Reading frame correction by targeted genome editing restores dystrophin expression in cells from Duchenne muscular dystrophy patients. Mol Ther 21:1718–1726

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pabo CO, Peisach E, Grant RA (2001) Design and selection of novel Cys2His2 zinc finger proteins. Annu Rev Biochem 70:313–340

    CAS  PubMed  Google Scholar 

  • Park CY, Kim J, Kweon J, Son JS, Lee JS, Yoo JE, Cho SR, Kim JH, Kim JS, Kim DW (2014) Targeted inversion and reversion of the blood coagulation factor 8 gene in human iPS cells using TALENs. Proc Natl Acad Sci U S A 111:9253–9258

    CAS  PubMed Central  PubMed  Google Scholar 

  • Perez EE, Wang J, Miller JC, Jouvenot Y, Kim KA, Liu O, Wang N, Lee G, Bartsevich VV, Lee Y-L, Guschin DY, Rupniewski I, Waite AJ, Carpenito C, Carroll RG, Orange JS, Urnov FD, Rebar EJ, Ando D, Gregory PD, Riley JL, Holmes MC, June CH (2008) Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nat Biotechnol 26:808–816

    CAS  PubMed Central  PubMed  Google Scholar 

  • Perez-Pinera P, Kocak DD, Vockley CM, Adler AF, Kabadi AM, Polstein LR, Thakore PI, Glass KA, Ousterout DG, Leong KW, Guilak F, Crawford GE, Reddy TE, Gersbach CA (2013) RNA-guided gene activation by CRISPR-Cas9-based transcription factors. Nat Methods 10:973–976

    CAS  PubMed Central  PubMed  Google Scholar 

  • Phang R-Z, Tay FC, Goh S-L, Lau C-H, Zhu H, Tan W-K, Liang Q, Chen C, Du S, Li Z, Tay JC-K, Wu C, Zeng J, Fan W, Toh HC, Wang S (2013) Zinc finger nuclease-expressing baculoviral vectors mediate targeted genome integration of reprogramming factor genes to facilitate the generation of human induced pluripotent stem cells. Stem Cells Transl Med 2:935–945

    CAS  PubMed Central  PubMed  Google Scholar 

  • Provasi E, Genovese P, Lombardo A, Magnani Z, Liu P, Reik A, Chu V, Paschon D, Zhang L, Kuball J, Camisa B, Bondanza A, Casorati G, Ponzoni M, Ciceri F, Bordignon C, Greenberg P, Holmes M, Gregory P, Naldini L, Bonini C (2012) Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer. Nat Med 18:807–815

    CAS  PubMed  Google Scholar 

  • Qi LS, Larson MH, Gilbert LA, Doudna JA, Weissman JS, Arkin AP, Lim WA (2013) Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell 152:1173–1183

    CAS  PubMed Central  PubMed  Google Scholar 

  • Qian K, Huang CL, Chen H, Blackbourn LW 4th, Chen Y, Cao J, Yao L, Sauvey C, Du Z, Zhang SC (2014) A simple and efficient system for regulating gene expression in human pluripotent stem cells and derivatives. Stem Cells 32:1230–1238

    CAS  PubMed  Google Scholar 

  • Ramakrishna S, Kwaku Dad A-B, Beloor J, Gopalappa R, Lee S-K, Kim H (2014) Gene disruption by cell-penetrating peptide-mediated delivery of Cas9 protein and guide RNA. Genome Res 24:1020–1027

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ran FA, Hsu PD, Lin C-Y, Gootenberg JS, Konermann S, Trevino AE, Scott DA, Inoue A, Matoba S, Zhang Y, Zhang F (2013) Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell 154:1380–1389

    CAS  PubMed  Google Scholar 

  • Reyon D, Tsai SQ, Khayter C, Foden JA, Sander JD, Joung JK (2012) FLASH assembly of TALENs for high-throughput genome editing. Nat Biotechnol 30:460–465

    CAS  PubMed Central  PubMed  Google Scholar 

  • Río P, Baños R, Lombardo A, Quintana-Bustamante O, Alvarez L, Garate Z, Genovese P, Almarza E, Valeri A, Díez B, Navarro S, Torres Y, Trujillo JP, Murillas R, Segovia JC, Samper E, Surrallés J, Gregory PD, Holmes MC, Naldini L, Bueren JA (2014) Targeted gene therapy and cell reprogramming in Fanconi anemia. EMBO Mol Med 6:835–848

    PubMed Central  PubMed  Google Scholar 

  • Rouet P, Smih F, Jasin M (1994a) Expression of a site-specific endonuclease stimulates homologous recombination in mammalian cells. Proc Natl Acad Sci U S A 91:6064–6068

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rouet P, Smih F, Jasin M (1994b) Introduction of double-strand breaks into the genome of mouse cells by expression of a rare-cutting endonuclease. Mol Cell Biol 14:8096–8106

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rousseau J, Chapdelaine P, Boisvert S, Almeida LP, Corbeil J, Montpetit A, Tremblay JP (2011) Endonucleases: tools to correct the dystrophin gene. J Gene Med 13:522–537

    CAS  PubMed  Google Scholar 

  • Ruby KM, Zheng B (2009) Gene targeting in a HUES line of human embryonic stem cells via electroporation. Stem Cells 27:1496–1506

    CAS  PubMed  Google Scholar 

  • Rusk N (2014) CRISPRs and epigenome editing. Nat Methods 11:28

    CAS  PubMed  Google Scholar 

  • Sadowski I, Ma J, Triezenberg S, Ptashne M (1988) GAL4-VP16 is an unusually potent transcriptional activator. Nature 335:563–564

    CAS  PubMed  Google Scholar 

  • Sakuma T, Hosoi S, Woltjen K, Suzuki K-I, Kashiwagi K, Wada H, Ochiai H, Miyamoto T, Kawai N, Sasakura Y, Matsuura S, Okada Y, Kawahara A, Hayashi S, Yamamoto T (2013) Efficient TALEN construction and evaluation methods for human cell and animal applications. Genes Cells 18:315–326

    CAS  PubMed  Google Scholar 

  • Sakuma T, Nishikawa A, Kume S, Chayama K, Yamamoto T (2014) Multiplex genome engineering in human cells using all-in-one CRISPR/Cas9 vector system. Sci Rep 4:5400

    PubMed Central  PubMed  Google Scholar 

  • Scherer WF, Syverton JT, Gey GO (1953) Studies on the propagation in vitro of poliomyelitis viruses. IV. Viral multiplication in a stable strain of human malignant epithelial cells (strain HeLa) derived from an epidermoid carcinoma of the cervix. J Exp Med 97:695–710

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schwank G, Koo B-K, Sasselli V, Dekkers JF, Heo I, Demircan T, Sasaki N, Boymans S, Cuppen E, van der Ent CK, Nieuwenhuis EES, Beekman JM, Clevers H (2013) Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell 13:653–658

    CAS  PubMed  Google Scholar 

  • Sebastiano V, Maeder ML, Angstman JF, Haddad B, Khayter C, Yeo DT, Goodwin MJ, Hawkins JS, Ramirez CL, Batista LFZ, Artandi SE, Wernig M, Joung JK (2011) In situ genetic correction of the sickle cell anemia mutation in human induced pluripotent stem cells using engineered zinc finger nucleases. Stem Cells 29:1717–1726

    CAS  PubMed Central  PubMed  Google Scholar 

  • Segal DJ, Dreier B, Beerli RR, Barbas CF 3rd (1999) Toward controlling gene expression at will: selection and design of zinc finger domains recognizing each of the 5′-GNN-3′ DNA target sequences. Proc Natl Acad Sci U S A 96:2758–2763

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shalem O, Sanjana NE, Hartenian E, Shi X, Scott DA, Mikkelsen TS, Heckl D, Ebert BL, Root DE, Doench JG, Zhang F (2014) Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343:84–87

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shen B, Zhang W, Zhang J, Zhou J, Wang J, Chen L, Wang L, Hodgkins A, Iyer V, Huang X, Skarnes WC (2014) Efficient genome modification by CRISPR-Cas9 nickase with minimal off-target effects. Nat Methods 11:399–402

    CAS  PubMed  Google Scholar 

  • Silva GH, Dalgaard JZ, Belfort M, Van Roey P (1999) Crystal structure of the thermostable archaeal intron-encoded endonuclease I-DmoI. J Mol Biol 286:1123–1136

    CAS  PubMed  Google Scholar 

  • Smith J, Bibikova M, Whitby FG, Reddy AR, Chandrasegaran S, Carroll D (2000) Requirements for double-strand cleavage by chimeric restriction enzymes with zinc finger DNA-recognition domains. Nucleic Acids Res 28:3361–3369

    CAS  PubMed Central  PubMed  Google Scholar 

  • Smithies O, Gregg RG, Boggs SS, Koralewski MA, Kucherlapati RS (1985) Insertion of DNA sequences into the human chromosomal beta-globin locus by homologous recombination. Nature 317:230–234

    CAS  PubMed  Google Scholar 

  • Soldner F, Laganière J, Cheng AW, Hockemeyer D, Gao Q, Alagappan R, Khurana V, Golbe LI, Myers RH, Lindquist S, Zhang L, Guschin D, Fong LK, Vu BJ, Meng X, Urnov FD, Rebar EJ, Gregory PD, Zhang HS, Jaenisch R (2011) Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations. Cell 146:318–331

    CAS  PubMed Central  PubMed  Google Scholar 

  • Song H, Chung S-K, Xu Y (2010) Modeling disease in human ESCs using an efficient BAC-based homologous recombination system. Cell Stem Cell 6:80–89

    CAS  PubMed  Google Scholar 

  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    CAS  PubMed  Google Scholar 

  • Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    CAS  PubMed  Google Scholar 

  • Tay FC, Tan W-K, Goh S-L, Ramachandra CJA, Lau C-H, Zhu H, Chen C, Du S, Phang R-Z, Shahbazi M, Fan W, Wang S (2013) Targeted transgene insertion into the AAVS1 locus driven by baculoviral vector-mediated zinc finger nuclease expression in human-induced pluripotent stem cells. J Gene Med 15:384–395

    CAS  PubMed  Google Scholar 

  • Tebas P, Stein D, Tang WW, Frank I, Wang SQ, Lee G, Spratt SK, Surosky RT, Giedlin MA, Nichol G, Holmes MC, Gregory PD, Ando DG, Kalos M, Collman RG, Binder-Scholl G, Plesa G, Hwang WT, Levine BL, June CH (2014) Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N Engl J Med 370:901–910

    CAS  PubMed Central  PubMed  Google Scholar 

  • Thomas KR, Capecchi MR (1987) Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51:503–512

    CAS  PubMed  Google Scholar 

  • Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147

    CAS  PubMed  Google Scholar 

  • Torikai H, Reik A, Liu P, Zhou Y, Zhang L, Maiti S, Huls H, Miller J, Kebriaei P, Rabinovitch B, Lee D, Champlin R, Bonini C, Naldini L, Rebar E, Gregory P, Holmes M, Cooper L (2012) A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR. Blood 119:5697–5705

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tsai SQ, Wyvekens N, Khayter C, Foden JA, Thapar V, Reyon D, Goodwin MJ, Aryee MJ, Joung JK (2014) Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing. Nat Biotechnol 32:569–576

    CAS  PubMed Central  PubMed  Google Scholar 

  • Urbach A, Schuldiner M, Benvenisty N (2004) Modeling for Lesch-Nyhan disease by gene targeting in human embryonic stem cells. Stem Cells 22:635–641

    CAS  PubMed  Google Scholar 

  • Urnov FD, Miller JC, Lee Y-L, Beausejour CM, Rock JM, Augustus S, Jamieson AC, Porteus MH, Gregory PD, Holmes MC (2005) Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature 435:646–651

    CAS  PubMed  Google Scholar 

  • Voigt P, Reinberg D (2013) Epigenome editing. Nat Biotechnol 31:1097–1099

    CAS  PubMed  Google Scholar 

  • Wang Y, Zhang WY, Hu S, Lan F, Lee AS, Huber B, Lisowski L, Liang P, Huang M, de Almeida PE, Won JH, Sun N, Robbins RC, Kay MA, Urnov FD, Wu JC (2012) Genome editing of human embryonic stem cells and induced pluripotent stem cells with zinc finger nucleases for cellular imaging. Circ Res 111:1494–1503

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang T, Wei JJ, Sabatini DM, Lander ES (2014) Genetic screens in human cells using the CRISPR-Cas9 system. Science 343:80–84

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yao Y, Nashun B, Zhou T, Qin L, Qin L, Zhao S, Xu J, Esteban M, Chen X (2011) Generation of CD34+ cells from CCR5-disrupted human embryonic and induced pluripotent stem cells. Hum Gene Ther 23:238–242

    PubMed  Google Scholar 

  • Ye L, Wang J, Beyer AI, Teque F, Cradick TJ, Qi Z, Chang JC, Bao G, Muench MO, Yu J, Levy JA, Kan YW (2014) Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5Delta32 mutation confers resistance to HIV infection. Proc Natl Acad Sci U S A 111:9591–9596

    CAS  PubMed  Google Scholar 

  • Yusa K, Rashid ST, Strick-Marchand H, Varela I, Liu P-Q, Paschon DE, Miranda E, Ordóñez A, Hannan NRF, Rouhani FJ, Darche S, Alexander G, Marciniak SJ, Fusaki N, Hasegawa M, Holmes MC, Di Santo JP, Lomas DA, Bradley A, Vallier L (2011) Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells. Nature 478:391–394

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhou Y, Zhu S, Cai C, Yuan P, Li C, Huang Y, Wei W (2014) High-throughput screening of a CRISPR/Cas9 library for functional genomics in human cells. Nature 509:487–491

    CAS  PubMed  Google Scholar 

  • Zhu H, Lau C-H, Goh S-L, Liang Q, Chen C, Du S, Phang R-Z, Tay FC, Tan W-K, Li Z, Tay JC-K, Fan W, Wang S (2013) Baculoviral transduction facilitates TALEN-mediated targeted transgene integration and Cre/LoxP cassette exchange in human-induced pluripotent stem cells. Nucleic Acids Res 41:e180

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zou J, Maeder ML, Mali P, Pruett-Miller SM, Thibodeau-Beganny S, Chou B-K, Chen G, Ye Z, Park I-H, Daley GQ, Porteus MH, Joung JK, Cheng L (2009) Gene targeting of a disease-related gene in human induced pluripotent stem and embryonic stem cells. Cell Stem Cell 5:97–110

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zou J, Mali P, Huang X, Dowey SN, Cheng L (2011a) Site-specific gene correction of a point mutation in human iPS cells derived from an adult patient with sickle cell disease. Blood 118:4599–4608

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zou J, Sweeney CL, Chou BK, Choi U, Pan J, Wang H, Dowey SN, Cheng L, Malech HL (2011b) Oxidase-deficient neutrophils from X-linked chronic granulomatous disease iPS cells: functional correction by zinc finger nuclease-mediated safe harbor targeting. Blood 117:5561–5572

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zwaka TP, Thomson JA (2003) Homologous recombination in human embryonic stem cells. Nat Biotechnol 21:319–321

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Reprogramming Science, Centre for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan

    Hongmei Lisa Li & Akitsu Hotta

Authors
  1. Hongmei Lisa Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akitsu Hotta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Akitsu Hotta .

Editor information

Editors and Affiliations

  1. Department of Mathematical and Life Sciences, Hiroshima University, Higashi-Hiroshima, Hiroshima, Japan

    Takashi Yamamoto

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Japan

About this chapter

Cite this chapter

Li, H.L., Hotta, A. (2015). Editing Cultured Human Cells: From Cell Lines to iPS Cells. In: Yamamoto, T. (eds) Targeted Genome Editing Using Site-Specific Nucleases. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55227-7_3

Download citation

Publish with us

Policies and ethics

Search

Navigation