Advertisement

Precision Genome Editing in Human-Induced Pluripotent Stem Cells

  • Knut WoltjenEmail author
Chapter
Part of the Current Human Cell Research and Applications book series (CHCRA)

Abstract

The advent of human-induced pluripotent stem cell (hiPSC) technology enabled researchers to gain access to the various somatic cell types that comprise the human body, along with the underlying genetic code which details their function or dysfunction in normal and disease states, respectively. In vitro disease models based on patient-specific hiPSCs have already demonstrated great potential for elucidating disease mechanisms, drug discovery, and validation of cell replacement therapies. In certain cases, accurate recapitulation or rectification of the genetic causes of disease requires the ability to precisely modify just a single base of DNA among the billions present in the human genome. Together with recent advances in gene editing technologies such as programmable endonucleases, we are now able to re-create pathogenic mutations with base precision for more reliable disease models. Moreover, these combined methods have opened the door to scarless repair of disease alleles for the future of personal stem cell therapy.

Keywords

Human-induced pluripotent stem cell hiPSC Gene targeting Nuclease CRISPR/Cas9 HDR NHEJ MMEJ Disease model Gene correction Isogenic control 

Notes

Acknowledgments

I would like to acknowledge all those who have contributed to the rapid growth in the fields of induced pluripotency and gene editing and recognize their important works not cited here for the sake of brevity. This manuscript was funded in part by a grant to K.W. from the Japan Agency for Medical Research and Development (AMED, no. 18bm0804001h0002).

Competing Financial Interests

The authors declare no competing financial interests.

References

  1. 1.
    Takahashi K, Yamanaka S. A decade of transcription factor-mediated reprogramming to pluripotency. Nat Rev Mol Cell Biol. 2016;17(3):183–93.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Clevers H. Modeling development and disease with organoids. Cell. 2016;165:1586–97.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Kim J-H, Kurtz A, Yuan B-Z, Zeng F, Lomax G, Loring JF, Crook J, Ju JH, Clarke L, Inamdar MS, et al. Report of the international stem cell banking initiative workshop activity: current hurdles and progress in seed-stock banking of human pluripotent stem cells. Stem Cells Transl Med. 2017;6:1956–62.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Sakuma T, Woltjen K. Nuclease-mediated genome editing: at the front-line of functional genomics technology. Develop Growth Differ. 2014;56:2–13.CrossRefGoogle Scholar
  5. 5.
    Zeltner N, Studer L. Pluripotent stem cell-based disease modeling: current hurdles and future promise. Curr Opin Cell Biol. 2015;37:102–10.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Kim HS, Bernitz JM, Lee D-F, Lemischka IR. Genomic editing tools to model human diseases with isogenic pluripotent stem cells. Stem Cells Dev. 2014;23:2673–86.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Jasin M. Genetic manipulation of genomes with rare-cutting endonucleases. Trends Genet. 1996;12:224–8.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Pavletich NP, Pabo CO. Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A. Science. 1991;252:809–17.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Kim YG, Cha J, Chandrasegaran S. Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. Proc Natl Acad Sci U S A. 1996;93:1156–60.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Smith J, Bibikova M, Whitby FG, Reddy AR, Chandrasegaran S, Carroll D. Requirements for double-strand cleavage by chimeric restriction enzymes with zinc finger DNA-recognition domains. Nucleic Acids Res. 2000;28:3361–9.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Elrod-Erickson M, Rould MA, Nekludova L, Pabo CO. Zif268 protein-DNA complex refined at 1.6 A: a model system for understanding zinc finger-DNA interactions. Structure. 1996;4:1171–80.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Hockemeyer D, Soldner F, Beard C, Gao Q, Mitalipova M, Dekelver RC, Katibah GE, Amora R, Boydston EA, Zeitler B, et al. Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases. Nat Biotechnol. 2009;27:851–7.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Boch J, Scholze H, Schornack S, Landgraf A, Hahn S, Kay S, Lahaye T, Nickstadt A, Bonas U. Breaking the code of DNA binding specificity of TAL-type III effectors. Science. 2009;326:1509–12.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Moscou MJ, Bogdanove AJ. A simple cipher governs DNA recognition by TAL effectors. Science. 2009;326:1501.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Christian M, Cermak T, Doyle EL, Schmidt C, Zhang F, Hummel A, Bogdanove AJ, Voytas DF. Targeting DNA double-strand breaks with TAL effector nucleases. Genetics. 2010;186:757–61.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Hockemeyer D, Wang H, Kiani S, Lai CS, Gao Q, Cassady JP, Cost GJ, Zhang L, Santiago Y, Miller JC, et al. Genetic engineering of human pluripotent cells using TALE nucleases. Nat Biotechnol. 2011;29(8):731–4.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Pattanayak V, Guilinger JP, Liu DR. Determining the specificities of TALENs, Cas9, and other genome-editing enzymes. Methods Enzymol. 2014;546:47–78.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    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;337:816–21.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. Genome engineering using the CRISPR-Cas9 system. Nat Protoc. 2013;8:2281–308.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, Norville JE, Church GM. RNA-guided human genome engineering via Cas9. Science. 2013;339(6121):823–6.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Koonin EV, Makarova KS, Zhang F. Diversity, classification and evolution of CRISPR-Cas systems. Curr Opin Microbiol. 2017;37:67–78.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Lee JK, Jeong E, Lee J, Jung M, Shin E, Kim Y-H, Lee K, Jung I, Kim D, Kim S, et al. Directed evolution of CRISPR-Cas9 to increase its specificity. Nat Commun. 2018;9:3048.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Hirano S, Nishimasu H, Ishitani R, Nureki O. Structural basis for the altered PAM specificities of engineered CRISPR-Cas9. Mol Cell. 2016;61:886–94.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Kleinstiver BP, Pattanayak V, Prew MS, Tsai SQ, Nguyen NT, Zheng Z, Joung JK. High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Nature. 2016;529:490–5.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Kleinstiver BP, Prew MS, Tsai SQ, Topkar VV, Nguyen NT, Zheng Z, Gonzales APW, Li Z, Peterson RT, Yeh J-RJ, et al. Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature. 2015;523:481–5.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Ceccaldi R, Rondinelli B, D’Andrea AD. Repair pathway choices and consequences at the double-strand break. Trends Cell Biol. 2016;26:52–64.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Mansour SL, Thomas KR, Capecchi MR. Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Nature. 1988;336:348–52.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Smithies O, Gregg RG, Boggs SS, Koralewski MA, Kucherlapati RS. Insertion of DNA sequences into the human chromosomal beta-globin locus by homologous recombination. Nature. 1985;317:230–4.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Thomas KR, Folger KR, Capecchi MR. High frequency targeting of genes to specific sites in the mammalian genome. Cell. 1986;44:419–28.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Shibata A, Moiani D, Arvai AS, Perry J, Harding SM, Genois M-M, Maity R, van Rossum-Fikkert S, Kertokalio A, Romoli F, et al. DNA double-Strand break repair pathway choice is directed by distinct MRE11 nuclease activities. Mol Cell. 2014;53:7–18.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Song F, Stieger K. Optimizing the DNA donor template for homology-directed repair of double-strand breaks. Mol Ther Nucleic Acid. 2017;7:53–60.CrossRefGoogle Scholar
  32. 32.
    Nakajima K, Zhou Y, Tomita A, Hirade Y, Gurumurthy CB, Nakada S. Precise and efficient nucleotide substitution near genomic nick via noncanonical homology-directed repair. Genome Res. 2018;28:223–30.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Miura H, Quadros RM, Gurumurthy CB, Ohtsuka M. Easi-CRISPR for creating knock-in and conditional knockout mouse models using long ssDNA donors. Nat Protoc. 2017;13:195–215.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Chen F, Pruett-Miller SM, Huang Y, Gjoka M, Duda K, Taunton J, Collingwood TN, Frodin M, Davis GD. High-frequency genome editing using ssDNA oligonucleotides with zinc-finger nucleases. Nat Meth. 2011;8:753–5.CrossRefGoogle Scholar
  35. 35.
    Merkert S, Wunderlich S, Bednarski C, Beier J, Haase A, Dreyer A-K, Schwanke K, Meyer J, Göhring G, Cathomen T, et al. Efficient designer nuclease-based homologous recombination enables direct PCR screening for footprintless targeted human pluripotent stem cells. Stem Cell Reports. 2014;2:107–18.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Orlando SJ, Santiago Y, Dekelver RC, Freyvert Y, Boydston EA, Moehle EA, Choi VM, Gopalan SM, Lou JF, Li J, et al. Zinc-finger nuclease-driven targeted integration into mammalian genomes using donors with limited chromosomal homology. Nucleic Acids Res. 2010;38:e152.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Radecke S, Radecke F, Cathomen T, Schwarz K. Zinc-finger nuclease-induced gene repair with oligodeoxynucleotides: wanted and unwanted target locus modifications. Mol Ther. 2010;18:743–53.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Soldner F, Laganière J, Cheng AW, Hockemeyer D, Gao Q, Alagappan R, Khurana V, Golbe LI, Myers RH, Lindquist S, et al. Generation of isogenic pluripotent stem cells differing exclusively at two early onset parkinson point mutations. Cell. 2011;146:318–31.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Richardson CD, Ray GJ, DeWitt MA, Curie GL, Corn JE. Enhancing homology-directed genome editing by catalytically active and inactive CRISPR-Cas9 using asymmetric donor DNA. Nat Biotechnol. 2016;34(3):339–44.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Liang X, Potter J, Kumar S, Ravinder N, Chesnut JD. Enhanced CRISPR/Cas9-mediated precise genome editing by improved design and delivery of gRNA, Cas9 nuclease, and donor DNA. J Biotechnol. 2017;241:136–46.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Liu Z, Hui Y, Shi L, Chen Z, Xu X, Chi L, Fan B, Fang Y, Liu Y, Ma L, et al. Efficient CRISPR/Cas9-mediated versatile, predictable, and donor-free gene knockout in human pluripotent stem cells. Stem Cell Reports. 2016;7:496–507.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Deng SK, Gibb B, de Almeida MJ, Greene EC, Symington LS. RPA antagonizes microhomology-mediated repair of DNA double-strand breaks. Nat Struct Mol Biol. 2014;21:405–12.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Kent T, Chandramouly G, McDevitt SM, Ozdemir AY, Pomerantz RT. Mechanism of microhomology-mediated end-joining promoted by human DNA polymerase θ. Nat Struct Mol Biol. 2015;22:230–7.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    McVey M, Lee SE. MMEJ repair of double-strand breaks (director’s cut): deleted sequences and alternative endings. Trends Genet. 2008;24:529–38.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    van Overbeek M, Capurso D, Carter MM, Thompson MS, Frias E, Russ C, Reece-Hoyes JS, Nye C, Gradia S, Vidal B, et al. DNA repair profiling reveals nonrandom outcomes at Cas9-mediated breaks. Mol Cell. 2016;63(4):633–46.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Allen FR, Crepaldi LR, Alsinet-Armengol C, Strong A, Kleshchevnikov V, De Angeli P, Palenikova P, Kosicki M, Bassett AR, Harding H, et al. Mutations generated by repair of Cas9-induced double strand breaks are predictable from surrounding sequence. bioRxiv. 2018:400341.  https://doi.org/10.1101/400341.
  47. 47.
    Taheri-Ghahfarokhi A, Taylor BJM, Nitsch R, Lundin A, Cavallo A-L, Madeyski-Bengtson K, Karlsson F, Clausen M, Hicks R, Mayr LM, et al. Decoding non-random mutational signatures at Cas9 targeted sites. Nucleic Acids Res. 2018;46:8417–34.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Ata H, Ekstrom TL, Martínez-Gálvez G, Mann CM, Dvornikov AV, Schaefbauer KJ, Ma AC, Dobbs D, Clark KJ, Ekker SC. Robust activation of microhomology-mediated end joining for precision gene editing applications. PLoS Genet. 2018;14:e1007652.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Bae S, Kweon J, Kim HS, Kim J-S. Microhomology-based choice of Cas9 nuclease target sites. Nat Methods. 2014;11:705–6.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Hindley C, Philpott A. The cell cycle and pluripotency. Biochem J. 2013;451:135–43.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Lin S, Staahl BT, Alla RK, Doudna JA. Enhanced homology-directed human genome engineering by controlled timing of CRISPR/Cas9 delivery. elife. 2014;3:e04766.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Yu C, Liu Y, Ma T, Liu K, Xu S, Zhang Y, Liu H, La Russa M, Xie M, Ding S, et al. Small molecules enhance CRISPR genome editing in pluripotent stem cells. Cell Stem Cell. 2015;16:142–7.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Canny MD, Moatti N, Wan LCK, Fradet-Turcotte A, Krasner D, Mateos-Gomez PA, Zimmermann M, Orthwein A, Juang Y-C, Zhang W, et al. Inhibition of 53BP1 favors homology-dependent DNA repair and increases CRISPR–Cas9 genome-editing efficiency. Nat Biotechnol. 2017;36:95–102.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Chu VT, Weber T, Wefers B, Wurst W, Sander S, Rajewsky K, Kühn R. Increasing the efficiency of homology-directed repair for CRISPR-Cas9-induced precise gene editing in mammalian cells. Nat Biotechnol. 2015;33:543–8.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Gutschner T, Haemmerle M, Genovese G, Draetta GF, Chin L. Post-translational regulation of Cas9 during G1 enhances homology-directed repair. Cell Rep. 2016;14:1555–66.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Charpentier M, Khedher AHY, Menoret S, Brion A, Lamribet K, Dardillac E, Boix C, Perrouault L, Tesson L, Geny S, et al. CtIP fusion to Cas9 enhances transgene integration by homology-dependent repair. Nat Commun. 2018;9(1):1133.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Nakade S, Mochida K, Kunii A, Nakamae K, Aida T, Tanaka K, Sakamoto N, Sakuma T, Yamamoto T. Biased genome editing using the local accumulation of DSB repair molecules system. Nat Commun. 2018;9(1):3270.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Liang X, Potter J, Kumar S, Zou Y, Quintanilla R, Sridharan M, Carte J, Chen W, Roark N, Ranganathan S, et al. Rapid and highly efficient mammalian cell engineering via Cas9 protein transfection. J Biotechnol. 2015;208:44–53.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Gonzalez F, Zhu Z, Shi Z-D, Lelli K, Verma N, Li QV, Huangfu D. An iCRISPR platform for rapid, multiplexable, and inducible genome editing in human pluripotent stem cells. Cell Stem Cell. 2014;15(2):215–26.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Zhu Z, Verma N, Gonzalez F, Shi Z-D, Huangfu D. A CRISPR/Cas-mediated selection-free knockin strategy in human embryonic stem cells. Stem Cell Reports. 2015;4:1103–11.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Oceguera-Yanez F, Kim S-I, Matsumoto T, Tan GW, Xiang L, Hatani T, Kondo T, Ikeya M, Yoshida Y, Inoue H, et al. Engineering the AAVS1 locus for consistent and scalable transgene expression in human iPSCs and their differentiated derivatives. Methods. 2016;101:43–55.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Wang G, Yang L, Grishin D, Rios X, Ye LY, Hu Y, Li K, Zhang D, Church GM, Pu WT. Efficient, footprint-free human iPSC genome editing by consolidation of Cas9/CRISPR and piggyBac technologies. Nat Protoc. 2017;12:88–103.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Woltjen K, Michael IP, Mohseni P, Desai R, Mileikovsky M, Hämäläinen R, Cowling R, Wang W, Liu P, Gertsenstein M, et al. piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature. 2009;458:766–70.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Steyer B, Bu Q, Cory E, Jiang K, Duong S, Sinha D, Steltzer S, Gamm D, Chang Q, Saha K. Scarless genome editing of human pluripotent stem cells via transient puromycin selection. Stem Cell Reports. 2018;10(2):642–54.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Lonowski LA, Narimatsu Y, Riaz A, Delay CE, Yang Z, Niola F, Duda K, Ober EA, Clausen H, Wandall HH, et al. Genome editing using FACS enrichment of nuclease-expressing cells and indel detection by amplicon analysis. Nat Protoc. 2017;12:581–603.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Arribere JA, Bell RT, Fu BXH, Artiles KL, Hartman PS, Fire AZ. Efficient marker-free recovery of custom genetic modifications with CRISPR/Cas9 in Caenorhabditis elegans. Genetics. 2014;198:837–46.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Liao S, Tammaro M, Yan H. Enriching CRISPR-Cas9 targeted cells by co-targeting the HPRT gene. Nucleic Acids Res. 2015;43:e134.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Mitzelfelt KA, McDermott-Roe C, Grzybowski MN, Marquez M, Kuo C-T, Riedel M, Lai S, Choi MJ, Kolander KD, Helbling D, et al. Efficient precision genome editing in iPSCs via genetic co-targeting with selection. Stem Cell Reports. 2017;8:491–9.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Agudelo D, Duringer A, Bozoyan L, Huard CC, Carter S, Loehr J, Synodinou D, Drouin M, Salsman J, Dellaire G, et al. Marker-free coselection for CRISPR-driven genome editing in human cells. Nat Methods. 2017;14(6):615–20.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Findlay SD, Vincent KM, Berman JR, Postovit L-M. A digital PCR-based method for efficient and highly specific screening of genome edited cells. PLoS One. 2016;11:e0153901.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Miyaoka Y, Chan AH, Judge LM, Yoo J, Huang M, Nguyen TD, Lizarraga PP, So P-L, Conklin BR. Isolation of single-base genome-edited human iPS cells without antibiotic selection. Nat Methods. 2014;11:291–3.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Capecchi MR. Gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century. Nat Rev Genet. 2005;6:507–12.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Hatada S, Arnold LW, Hatada T, Cowhig JE, Ciavatta D, Smithies O. Isolating gene-corrected stem cells without drug selection. Proc Natl Acad Sci U S A. 2005;102:16357–61.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Deyle DR, Li LB, Ren G, Russell DW. The effects of polymorphisms on human gene targeting. Nucleic Acids Res. 2014;42:3119–24.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Yang L, Güell M, Byrne S, Yang JL, De Los Angeles A, Mali P, Aach J, Kim-Kiselak C, Briggs AW, Rios X, et al. Optimization of scarless human stem cell genome editing. Nucleic Acids Res. 2013;41:9049–61.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Iiizumi S, Nomura Y, So S, Uegaki K, Aoki K, Shibahara K-i, Adachi N, Koyama H. Simple one-week method to construct gene-targeting vectors: application to production of human knockout cell lines. BioTechniques. 2006;41:311–6.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Pham CT, MacIvor DM, Hug BA, Heusel JW, Ley TJ. Long-range disruption of gene expression by a selectable marker cassette. Proc Natl Acad Sci U S A. 1996;93:13090–5.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Araki K, Imaizumi T, Okuyama K, Oike Y, Yamamura K. Efficiency of recombination by Cre transient expression in embryonic stem cells: comparison of various promoters. J Biochem. 1997;122:977–82.PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Davis RP, Costa M, Grandela C, Holland AM, Hatzistavrou T, Micallef SJ, Li X, Goulburn AL, Azzola L, Elefanty AG, et al. A protocol for removal of antibiotic resistance cassettes from human embryonic stem cells genetically modified by homologous recombination or transgenesis. Nat Protoc. 2008;3:1550–8.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Crane AM, Kramer P, Bui JH, Chung WJ, Li XS, Gonzalez-Garay ML, Hawkins F, Liao W, Mora D, Choi S, et al. Targeted correction and restored function of the CFTR gene in cystic fibrosis induced pluripotent stem cells. Stem Cell Reports. 2015;4:569–77.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Zou J, Mali P, Huang X, Dowey SN, Cheng L. Site-specific gene correction of a point mutation in human iPS cells derived from an adult patient with sickle cell disease. Blood. 2011;118:4599–608.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Sebastiano V, Zhen HH, Haddad B, Derafshi BH, Bashkirova E, Melo SP, Wang P, Leung TL, Siprashvili Z, Tichy A, et al. Human COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa. Sci Transl Med. 2014;6:264ra163.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Kondo T, Imamura K, Funayama M, Tsukita K, Miyake M, Ohta A, Woltjen K, Nakagawa M, Asada T, Arai T, et al. iPSC-based compound screening and in vitro trials identify a synergistic anti-amyloid β combination for Alzheimer’s disease. Cell Rep. 2017;21(8):2304–12.PubMedCrossRefPubMedCentralGoogle Scholar
  84. 84.
    Meier ID, Bernreuther C, Tilling T, Neidhardt J, Wong YW, Schulze C, Streichert T, Schachner M. Short DNA sequences inserted for gene targeting can accidentally interfere with off-target gene expression. FASEB J. 2010;24:1714–24.PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Li X, Lobo N, Bauser CA, Fraser MJ Jr. The minimum internal and external sequence requirements for transposition of the eukaryotic transformation vector piggyBac. Mol Gen Genomics. 2001;266:190–8.CrossRefGoogle Scholar
  86. 86.
    Yusa K, Zhou L, Li MA, Bradley A, Craig NL. A hyperactive piggyBac transposase for mammalian applications. Proc Natl Acad Sci. 2011;108:1531–6.PubMedCrossRefPubMedCentralGoogle Scholar
  87. 87.
    Yusa K, Rashid ST, Strick-Marchand H, Varela I, Liu P-Q, Paschon DE, Miranda E, Ordóñez A, Hannan NRF, Rouhani FJ, et al. Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells. Nature. 2011;478:391–4.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Imamura K, Izumi Y, Watanabe A, Tsukita K, Woltjen K, Yamamoto T, Hotta A, Kondo T, Kitaoka S, Ohta A, et al. The Src/c-Abl pathway is a potential therapeutic target in amyotrophic lateral sclerosis. Sci Transl Med. 2017;9(391):eaaf3962.CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Xie F, Ye L, Chang JC, Beyer AI, Wang J, Muench MO, Kan YW. Seamless gene correction of β-thalassemia mutations in patient-specific iPSCs using CRISPR/Cas9 and piggyBac. Genome Res. 2014;24:1526–33.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Li X, Burnight ER, Cooney AL, Malani N, Brady T, Sander JD, Staber J, Wheelan SJ, Joung JK, McCray PB, et al. piggyBac transposase tools for genome engineering. Proc Natl Acad Sci. 2013;110:E2279–87.PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Kim S-I, Matsumoto T, Kagawa H, Nakamura M, Hirohata R, Ueno A, Ohishi M, Sakuma T, Soga T, Yamamoto T, et al. Microhomology-assisted scarless genome editing in human iPSCs. Nat Commun. 2018;9:939.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Sakuma T, Hosoi S, Woltjen K, Suzuki K-I, Kashiwagi K, Wada H, Ochiai H, Miyamoto T, Kawai N, Sasakura Y, et al. Efficient TALEN construction and evaluation methods for human cell and animal applications. Genes Cells. 2013;18:315–26.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Cermak T, Doyle EL, Christian M, Wang L, Zhang Y, Schmidt C, Baller JA, Somia NV, Bogdanove AJ, Voytas DF. Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting. Nucleic Acids Res. 2011;39:e82.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Kamatani N, Kuroshima S, Hakoda M, Palella TD, Hidaka Y. Crossovers within a short DNA sequence indicate a long evolutionary history of the APRT*J mutation. Hum Genet. 1990;85(6):600–4.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Lee S, Huh JY, Turner DM, Lee S, Robinson J, Stein JE, Shim SH, Hong CP, Kang MS, Nakagawa M, et al. Repurposing the cord blood Bank for haplobanking of HLA-homozygous iPSCs and their usefulness to multiple populations. Stem Cells. 2018;126:663.Google Scholar
  96. 96.
    Warren CR, O’Sullivan JF, Friesen M, Becker CE, Zhang X, Liu P, Wakabayashi Y, Morningstar JE, Shi X, Choi J, et al. Induced pluripotent stem cell differentiation enables functional validation of GWAS variants in metabolic disease. Cell Stem Cell. 2017;20:547–57.PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Hibaoui Y, Grad I, Letourneau A, Sailani MR, Dahoun S, Santoni FA, Gimelli S, Guipponi M, Pelte MF, Béna F, et al. Modelling and rescuing neurodevelopmental defect of Down syndrome using induced pluripotent stem cells from monozygotic twins discordant for trisomy 21. EMBO Mol Med. 2014;6:259–77.PubMedPubMedCentralGoogle Scholar
  98. 98.
    Zhang X-H, Tee LY, Wang X-G, Huang Q-S, Yang S-H. Off-target effects in CRISPR/Cas9-mediated genome engineering. Mol Ther Nucleic Acid. 2015;4:e264.CrossRefGoogle Scholar
  99. 99.
    Lessard S, Francioli L, Alfoldi J, Tardif J-C, Ellinor PT, MacArthur DG, Lettre G, Orkin SH, Canver MC. Human genetic variation alters CRISPR-Cas9 on- and off-targeting specificity at therapeutically implicated loci. Proc Natl Acad Sci. 2017;114:E11257–66.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Kim D, Bae S, Park J, Kim E, Kim S, Yu HR, Hwang J, Kim J-I, Kim J-S. Digenome-seq: genome-wide profiling of CRISPR-Cas9 off-target effects in human cells. Nat Methods. 2015;12:237–43.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Christie KA, Courtney DG, DeDionisio LA, Shern CC, Majumdar S, Mairs LC, Nesbit MA, Moore CBT. Towards personalised allele-specific CRISPR gene editing to treat autosomal dominant disorders. Sci Rep. 2017;7(1):16174.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Smith C, Abalde-Atristain L, He C, Brodsky BR, Braunstein EM, Chaudhari P, Jang Y-Y, Cheng L, Ye Z. Efficient and allele-specific genome editing of disease loci in human iPSCs. Mol Ther. 2015;23:570–7.PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    Hess GT, Tycko J, Yao D, Bassik MC. Methods and applications of CRISPR-mediated base editing in eukaryotic genomes. Mol Cell. 2017;68:26–43.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    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;533:420–4.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Nishida K, Arazoe T, Yachie N, Banno S, Kakimoto M, Tabata M, Mochizuki M, Miyabe A, Araki M, Hara KY, et al. Targeted nucleotide editing using hybrid prokaryotic and vertebrate adaptive immune systems. Science. 2016;353(6305):aaf8729.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Center for iPS Cell Research and Application (CiRA)Kyoto UniversityKyotoJapan
  2. 2.Hakubi Center for Advanced ResearchKyoto UniversityKyotoJapan

Personalised recommendations