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TALENs pp 27–42Cite as

The Development of TALE Nucleases for Biotechnology

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1338))

Abstract

The development of a facile genome engineering technology based on transcription activator-like effector nucleases (TALENs) has led to significant advances in diverse areas of science and medicine. In this review, we provide a broad overview of the development of TALENs and the use of this technology in basic science, biotechnology, and biomedical applications. This includes the discovery of DNA recognition by TALEs, engineering new TALE proteins to diverse targets, general advances in nuclease-based editing strategies, and challenges that are specific to various applications of the TALEN technology. We review examples of applying TALENs for studying gene function and regulation, generating disease models, and developing gene therapies. The current status of genome editing and future directions for other uses of these technologies are also discussed.

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References

  1. Perez-Pinera P, Ousterout DG, Gersbach CA (2012) Advances in targeted genome editing. Curr Opin Chem Biol 16(3–4):268–277

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Gaj T, Gersbach CA, Barbas CF III (2013) ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol 31(7):397–405

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Urnov FD, Rebar EJ, Holmes MC et al (2010) Genome editing with engineered zinc finger nucleases. Nat Rev Genet 11(9):636–646

    Article  CAS  PubMed  Google Scholar 

  4. Gersbach CA, Gaj T, Barbas CF III (2014) Synthetic zinc finger proteins: the advent of targeted gene regulation and genome modification technologies. Acc Chem Res 47:2309–2318

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Mussolino C, Cathomen T (2012) TALE nucleases: tailored genome engineering made easy. Curr Opin Biotechnol 23:644–650

    Article  CAS  PubMed  Google Scholar 

  6. Joung JK, Sander JD (2012) TALENs: a widely applicable technology for targeted genome editing. Nat Rev Mol Cell Biol 14(1):49–55

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  7. Sander JD, Joung JK (2014) CRISPR-Cas systems for editing, regulating and targeting genomes. Nat Biotechnol 32:347–355

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Cong L, Ran FA, Cox D et al (2013) Multiplex genome engineering using CRISPR/Cas systems. Science 339(6121):819–823

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Mali P, Yang L, Esvelt KM et al (2013) RNA-guided human genome engineering via Cas9. Science 339(6121):823–826

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Hockemeyer D, Wang H, Kiani S et al (2011) Genetic engineering of human pluripotent cells using TALE nucleases. Nat Biotechnol 29(8):731–734

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Mussolino C, Morbitzer R, Lütge F et al (2011) A novel TALE nuclease scaffold enables high genome editing activity in combination with low toxicity. Nucleic Acids Res 39(21):9283–9293

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Reyon D, Tsai SQ, Khayter C et al (2012) FLASH assembly of TALENs for high-throughput genome editing. Nat Biotechnol 30:460–465

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Cermak T, Doyle EL, Christian M et al (2011) Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting. Nucleic Acids Res 39(12):e82

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Moscou MJ, Bogdanove AJ (2009) A simple cipher governs DNA recognition by TAL effectors. Science 326(5959):1501

    Article  CAS  PubMed  Google Scholar 

  15. Boch J, Scholze H, Schornack S et al (2009) Breaking the code of DNA binding specificity of TAL-type III effectors. Science 326(5959):1509–1512

    Article  CAS  PubMed  Google Scholar 

  16. Cho SW, Kim S, Kim JM et al (2013) Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease. Nat Biotechnol 31(3):230–232

    Article  CAS  PubMed  Google Scholar 

  17. Hou Z, Zhang Y, Propson NE et al (2013) Efficient genome engineering in human pluripotent stem cells using Cas9 from Neisseria meningitidis. Proc Natl Acad Sci U S A 110(39):15644–15649

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Jinek M, East A, Cheng A et al (2013) RNA-programmed genome editing in human cells. eLife 2:e00471

    Article  PubMed Central  PubMed  Google Scholar 

  19. Horii T, Tamura D, Morita S et al (2013) Generation of an ICF syndrome model by efficient genome editing of human induced pluripotent stem cells using the CRISPR system. Int J Mol Sci 14(10):19774–19781

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  20. Yang L, Guell M, Byrne S et al (2013) Optimization of scarless human stem cell genome editing. Nucleic Acids Res 41(19):9049–9061

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Redondo P, Prieto J, Muñoz IG et al (2008) Molecular basis of xeroderma pigmentosum group C DNA recognition by engineered meganucleases. Nature 456(7218):107–111

    Article  CAS  PubMed  Google Scholar 

  22. Silva G, Poirot L, Galetto R et al (2011) Meganucleases and other tools for targeted genome engineering: perspectives and challenges for gene therapy. Curr Gene Ther 11(1):11–27

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Parekh-Olmedo H, Kmiec EB (2007) Progress and prospects: targeted gene alteration (TGA). Gene Ther 14(24):1675–1680

    Article  CAS  PubMed  Google Scholar 

  24. Gersbach CA, Gaj T, Gordley RM et al (2011) Targeted plasmid integration into the human genome by an engineered zinc-finger recombinase. Nucleic Acids Res 39(17):7868–7878

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Gaj T, Mercer AC, Gersbach CA et al (2011) Structure-guided reprogramming of serine recombinase DNA sequence specificity. Proc Natl Acad Sci U S A 108(2):498–503

    Article  PubMed Central  PubMed  Google Scholar 

  26. Gordley RM, Gersbach CA, Barbas CF III (2009) Synthesis of programmable integrases. Proc Natl Acad Sci U S A 106(13):5053–5058

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Gaj T, Mercer AC, Sirk SJ et al (2013) A comprehensive approach to zinc-finger recombinase customization enables genomic targeting in human cells. Nucleic Acids Res 41(6):3937–3946

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Mercer AC, Gaj T, Fuller RP et al (2012) Chimeric TALE recombinases with programmable DNA sequence specificity. Nucleic Acids Res 40(21):11163–11172

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Jarjour J, West-Foyle H, Certo MT et al (2009) High-resolution profiling of homing endonuclease binding and catalytic specificity using yeast surface display. Nucleic Acids Res 37(20):6871–6880

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Takeuchi R, Lambert AR, Mak AN et al (2011) Tapping natural reservoirs of homing endonucleases for targeted gene modification. Proc Natl Acad Sci U S A 108(32):13077–13082

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Takeuchi R, Choi M, Stoddard BL (2014) Redesign of extensive protein-DNA interfaces of meganucleases using iterative cycles of in vitro compartmentalization. Proc Natl Acad Sci U S A 111(11):4061–4066

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Boissel S, Jarjour J, Astrakhan A et al (2014) megaTALs: a rare-cleaving nuclease architecture for therapeutic genome engineering. Nucleic Acids Res 42(4):2591–2601

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Beurdeley M, Bietz F, Li J et al (2013) Compact designer TALENs for efficient genome engineering. Nat Commun 4:1762

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  34. Rivera-Torres N, Strouse B, Bialk P et al (2014) The position of DNA cleavage by TALENs and cell synchronization influences the frequency of gene editing directed by single-stranded oligonucleotides. PLoS One 9(5):e96483

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  35. Gaj T, Sirk SJ, Barbas CF III (2014) Expanding the scope of site-specific recombinases for genetic and metabolic engineering. Biotechnol Bioeng 111(1):1–15

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Rouet P, Smih F, Jasin M (1994) Introduction of double-strand breaks into the genome of mouse cells by expression of a rare-cutting endonuclease. Mol Cell Biol 14(12):8096–8106

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Rouet P, Smih F, Jasin M (1994) Expression of a site-specific endonuclease stimulates homologous recombination in mammalian cells. Proc Natl Acad Sci U S A 91(13):6064–6068

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Moehle EA, Rock JM, Lee Y-L et al (2007) Targeted gene addition into a specified location in the human genome using designed zinc finger nucleases. Proc Natl Acad Sci 104(9):3055–3060

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Urnov F, Miller J, Lee Y et al (2005) Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature 435:646–651

    Article  CAS  PubMed  Google Scholar 

  40. Sebastiano V, Maeder ML, Angstman JF et al (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(11):1717–1726

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Zou J, Mali P, Huang X et al (2011) Site-specific gene correction of a point mutation in human iPS cells derived from an adult patient with sickle cell disease. Blood 118(17):4599–4608

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Yusa K, Rashid ST, Strick-Marchand H et al (2011) Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells. Nature 478(7369):391–394

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Li H, Haurigot V, Doyon Y et al (2011) In vivo genome editing restores haemostasis in a mouse model of haemophilia. Nature 475(7355):217–221

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Perez EE, Wang J, Miller JC et al (2008) Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nat Biotechnol 26(7):808–816

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Holt N, Wang J, Kim K et al (2010) Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo. Nat Biotechnol 28(8):839–847

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Lee HJ, Kim E, Kim JS (2010) Targeted chromosomal deletions in human cells using zinc finger nucleases. Genome Res 20(1):81–89

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Gupta A, Hall VL, Kok FO et al (2013) Targeted chromosomal deletions and inversions in zebrafish. Genome Res 23(6):1008–1017

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Sollu C, Pars K, Cornu TI et al (2010) Autonomous zinc-finger nuclease pairs for targeted chromosomal deletion. Nucleic Acids Res 38(22):8269–8276

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  49. Chapdelaine P, Pichavant C, Rousseau J et al (2010) Meganucleases can restore the reading frame of a mutated dystrophin. Gene Ther 17(7):846–858

    Article  CAS  PubMed  Google Scholar 

  50. Ousterout DG, Perez-Pinera P, Thakore PI et al (2013) Reading frame correction by targeted genome editing restores dystrophin expression in cells from Duchenne muscular dystrophy patients. Mol Ther 21(9):1718–1726

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Mak AN, Bradley P, Cernadas RA et al (2012) The crystal structure of TAL effector PthXo1 bound to its DNA target. Science 335(6069):716–719

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Deng D, Yan C, Pan X et al (2012) Structural basis for sequence-specific recognition of DNA by TAL effectors. Science 335(6069):720–723

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Zhang F, Cong L, Lodato S et al (2011) Efficient construction of sequence-specific TAL effectors for modulating mammalian transcription. Nat Biotechnol 29(2):149–153

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  54. Christian M, Cermak T, Doyle EL et al (2010) Targeting DNA double-strand breaks with TAL effector nucleases. Genetics 186(2):757–761

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Miller JC, Tan S, Qiao G et al (2011) A TALE nuclease architecture for efficient genome editing. Nat Biotechnol 29(2):143–148

    Article  CAS  PubMed  Google Scholar 

  56. Doyle EL, Hummel AW, Demorest ZL et al (2013) TAL effector specificity for base 0 of the DNA target is altered in a complex, effector- and assay-dependent manner by substitutions for the tryptophan in cryptic repeat −1. PLoS One 8(12):e82120

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  57. Lamb BM, Mercer AC, Barbas CF III (2013) Directed evolution of the TALE N-terminal domain for recognition of all 5′ bases. Nucleic Acids Res 41(21):9779–9785

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Konermann S, Brigham MD, Trevino AE et al (2013) Optical control of mammalian endogenous transcription and epigenetic states. Nature 500(7463):472–476

    PubMed Central  CAS  PubMed  Google Scholar 

  59. Maeder ML, Angstman JF, Richardson ME et al (2013) Targeted DNA demethylation and activation of endogenous genes using programmable TALE-TET1 fusion proteins. Nat Biotechnol 31(12):1137–1142

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  60. Christian ML, Demorest ZL, Starker CG et al (2012) Targeting G with TAL effectors: a comparison of activities of TALENs constructed with NN and NK repeat variable di-residues. PLoS One 7(9):e45383

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Streubel J, Blucher C, Landgraf A et al (2012) TAL effector RVD specificities and efficiencies. Nat Biotechnol 30(7):593–595

    Article  CAS  PubMed  Google Scholar 

  62. Cong L, Zhou R, Kuo YC et al (2012) Comprehensive interrogation of natural TALE DNA-binding modules and transcriptional repressor domains. Nat Commun 3:968

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  63. Lin Y, Fine EJ, Zheng Z et al (2014) SAPTA: a new design tool for improving TALE nuclease activity. Nucleic Acids Res 42:e47

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  64. Doyle EL, Booher NJ, Standage DS et al (2012) TAL effector-nucleotide targeter (TALE-NT) 2.0: tools for TAL effector design and target prediction. Nucleic Acids Res 40(Web Server issue):W117–W122

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  65. Sander JD, Maeder ML, Reyon D et al (2010) ZiFiT (Zinc Finger Targeter): an updated zinc finger engineering tool. Nucleic Acids Res 38(Suppl 2):W462–W468

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  66. Fine EJ, Cradick TJ, Zhao CL et al (2014) An online bioinformatics tool predicts zinc finger and TALE nuclease off-target cleavage. Nucleic Acids Res 42(6):e42

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. Briggs AW, Rios X, Chari R et al (2012) Iterative capped assembly: rapid and scalable synthesis of repeat-module DNA such as TAL effectors from individual monomers. Nucleic Acids Res 40(15):e117

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Schmid-Burgk JL, Schmidt T, Kaiser V et al (2013) A ligation-independent cloning technique for high-throughput assembly of transcription activator-like effector genes. Nat Biotechnol 31(1):76–81

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. Bedell VM, Wang Y, Campbell JM et al (2012) In vivo genome editing using a high-efficiency TALEN system. Nature 491(7422):114–118

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  70. Sun N, Bao Z, Xiong X et al (2014) SunnyTALEN: a second-generation TALEN system for human genome editing. Biotechnol Bioeng 111:683–691

    Article  CAS  PubMed  Google Scholar 

  71. Miller JC, Holmes MC, Wang J et al (2007) An improved zinc-finger nuclease architecture for highly specific genome editing. Nat Biotechnol 25(7):778–785

    Article  CAS  PubMed  Google Scholar 

  72. Doyon Y, Vo TD, Mendel MC et al (2010) Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architectures. Nat Methods 8(1):74–79

    Article  PubMed  CAS  Google Scholar 

  73. Szczepek M, Brondani V, Buchel J et al (2007) Structure-based redesign of the dimerization interface reduces the toxicity of zinc-finger nucleases. Nat Biotechnol 25(7):786–793

    Article  CAS  PubMed  Google Scholar 

  74. Ramirez CL, Certo MT, Mussolino C et al (2012) Engineered zinc finger nickases induce homology-directed repair with reduced mutagenic effects. Nucleic Acids Res 40(12):5560–5568

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  75. Wang J, Friedman G, Doyon Y et al (2012) Targeted gene addition to a predetermined site in the human genome using a ZFN-based nicking enzyme. Genome Res 22(7):1316–1326

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  76. Guo J, Gaj T, Barbas C III (2010) Directed evolution of an enhanced and highly efficient FokI cleavage domain for zinc finger nucleases. J Mol Biol 400:96–107

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. de Lange O, Schreiber T, Schandry N et al (2013) Breaking the DNA-binding code of Ralstonia solanacearum TAL effectors provides new possibilities to generate plant resistance genes against bacterial wilt disease. New Phytol 199(3):773–786

    Article  PubMed  CAS  Google Scholar 

  78. Li L, Atef A, Piatek A et al (2013) Characterization and DNA-binding specificities of Ralstonia TAL-like effectors. Mol Plant 6(4):1318–1330

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  79. Bultmann S, Morbitzer R, Schmidt CS et al (2012) Targeted transcriptional activation of silent oct4 pluripotency gene by combining designer TALEs and inhibition of epigenetic modifiers. Nucleic Acids Res 40(12):5368–5377

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  80. Kim Y, Kweon J, Kim A et al (2013) A library of TAL effector nucleases spanning the human genome. Nat Biotechnol 31(3):251–258

    Article  CAS  PubMed  Google Scholar 

  81. Valton J, Dupuy A, Daboussi F et al (2012) Overcoming transcription activator-like effector (TALE) DNA binding domain sensitivity to cytosine methylation. J Biol Chem 287(46):38427–38432

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  82. Deng D, Yin P, Yan C et al (2012) Recognition of methylated DNA by TAL effectors. Cell Res 22(10):1502–1504

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  83. Perez-Pinera P, Ousterout DG, Brunger JM et al (2013) Synergistic and tunable human gene activation by combinations of synthetic transcription factors. Nat Methods 10(3):239–242

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  84. Holkers M, Maggio I, Liu J et al (2013) Differential integrity of TALE nuclease genes following adenoviral and lentiviral vector gene transfer into human cells. Nucleic Acids Res 41(5):e63

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  85. Liu J, Gaj T, Patterson JT et al (2014) Cell-penetrating peptide-mediated delivery of TALEN proteins via bioconjugation for genome engineering. PLoS One 9(1):e85755

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  86. Gaj T, Guo J, Kato Y et al (2012) Targeted gene knockout by direct delivery of zinc-finger nuclease proteins. Nat Methods 9(8):805–807

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  87. Ding Q, Lee YK, Schaefer EA et al (2013) A TALEN genome-editing system for generating human stem cell-based disease models. Cell Stem Cell 12(2):238–251

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  88. Kim YK, Wee G, Park J et al (2013) TALEN-based knockout library for human microRNAs. Nat Struct Mol Biol 20(12):1458–1464

    Article  CAS  PubMed  Google Scholar 

  89. Zhang Z, Xiang D, Heriyanto F et al (2013) Dissecting the roles of miR-302/367 cluster in cellular reprogramming using TALE-based repressor and TALEN. Stem Cell Reports 1(3):218–225

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  90. Wang H, Hu YC, Markoulaki S et al (2013) TALEN-mediated editing of the mouse Y chromosome. Nat Biotechnol 31(6):530–532

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  91. Takada S, Sato T, Ito Y et al (2013) Targeted gene deletion of miRNAs in mice by TALEN system. PLoS One 8(10):e76004

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  92. Tesson L, Usal C, Menoret S et al (2011) Knockout rats generated by embryo microinjection of TALENs. Nat Biotechnol 29(8):695–696

    Article  CAS  PubMed  Google Scholar 

  93. Carlson DF, Tan W, Lillico SG et al (2012) Efficient TALEN-mediated gene knockout in livestock. Proc Natl Acad Sci U S A 109(43):17382–17387

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  94. Sander JD, Cade L, Khayter C et al (2011) Targeted gene disruption in somatic zebrafish cells using engineered TALENs. Nat Biotechnol 29(8):697–698

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  95. Huang P, Xiao A, Zhou M et al (2011) Heritable gene targeting in zebrafish using customized TALENs. Nat Biotechnol 29(8):699–700

    Article  PubMed  CAS  Google Scholar 

  96. Lo TW, Pickle CS, Lin S et al (2013) Precise and heritable genome editing in evolutionarily diverse nematodes using TALENs and CRISPR/Cas9 to engineer insertions and deletions. Genetics 195(2):331–348

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  97. Wood AJ, Lo TW, Zeitler B et al (2011) Targeted genome editing across species using ZFNs and TALENs. Science 333(6040):307

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  98. Hayashi T, Sakamoto K, Sakuma T et al (2014) Transcription activator-like effector nucleases efficiently disrupt the target gene in Iberian ribbed newts (Pleurodeles waltl), an experimental model animal for regeneration. Dev Growth Differ 56(1):115–121

    Article  CAS  PubMed  Google Scholar 

  99. Ma S, Zhang S, Wang F et al (2012) Highly efficient and specific genome editing in silkworm using custom TALENs. PLoS One 7(9):e45035

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  100. Beumer KJ, Trautman JK, Christian M et al (2013) Comparing zinc finger nucleases and transcription activator-like effector nucleases for gene targeting in Drosophila. G3 (Bethesda) 3(10):1717–1725

    Article  CAS  Google Scholar 

  101. Smidler AL, Terenzi O, Soichot J et al (2013) Targeted mutagenesis in the malaria mosquito using TALE nucleases. PLoS One 8(8):e74511

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  102. Lei Y, Guo X, Liu Y et al (2012) Efficient targeted gene disruption in Xenopus embryos using engineered transcription activator-like effector nucleases (TALENs). Proc Natl Acad Sci U S A 109(43):17484–17489

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  103. Voytas DF (2013) Plant genome engineering with sequence-specific nucleases. Annu Rev Plant Biol 64:327–350

    Article  CAS  PubMed  Google Scholar 

  104. Mahfouz MM, Li L, Shamimuzzaman M et al (2011) De novo-engineered transcription activator-like effector (TALE) hybrid nuclease with novel DNA binding specificity creates double-strand breaks. Proc Natl Acad Sci U S A 108(6):2623–2628

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  105. Shan Q, Wang Y, Chen K et al (2013) Rapid and efficient gene modification in rice and Brachypodium using TALENs. Mol Plant 6(4):1365–1368

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  106. Christian M, Qi Y, Zhang Y et al (2013) Targeted mutagenesis of Arabidopsis thaliana using engineered TAL effector nucleases. G3 (Bethesda) 3(10):1697–1705

    Article  CAS  Google Scholar 

  107. Wendt T, Holm PB, Starker CG et al (2013) TAL effector nucleases induce mutations at a pre-selected location in the genome of primary barley transformants. Plant Mol Biol 83(3):279–285

    Article  CAS  PubMed  Google Scholar 

  108. Osborn MJ, Starker CG, McElroy AN et al (2013) TALEN-based gene correction for epidermolysis bullosa. Mol Ther 21(6):1151–1159

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  109. Sun N, Liang J, Abil Z et al (2012) Optimized TAL effector nucleases (TALENs) for use in treatment of sickle cell disease. Mol Biosyst 8(4):1255–1263

    Article  CAS  PubMed  Google Scholar 

  110. Voit RA, Hendel A, Pruett-Miller SM et al (2014) Nuclease-mediated gene editing by homologous recombination of the human globin locus. Nucleic Acids Res 42(2):1365–1378

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  111. Ma N, Liao B, Zhang H et al (2013) Transcription activator-like effector nuclease (TALEN)-mediated gene correction in integration-free beta-thalassemia induced pluripotent stem cells. J Biol Chem 288(48):34671–34679

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  112. Dupuy A, Valton J, Leduc S et al (2013) Targeted gene therapy of xeroderma pigmentosum cells using meganuclease and TALEN. PLoS One 8(11):e78678

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  113. Choi SM, Kim Y, Shim JS et al (2013) Efficient drug screening and gene correction for treating liver disease using patient-specific stem cells. Hepatology 57(6):2458–2468

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  114. Bacman SR, Williams SL, Pinto M et al (2013) Specific elimination of mutant mitochondrial genomes in patient-derived cells by mitoTALENs. Nat Med 19(9):1111–1113

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  115. Tebas P, Stein D, Tang WW et al (2014) Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N Engl J Med 370(10):901–910

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  116. Mussolino C, Alzubi J, Fine EJ et al (2014) TALENs facilitate targeted genome editing in human cells with high specificity and low cytotoxicity. Nucleic Acids Res 42(10):6762–6773

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  117. Ye L, Wang J, Beyer AI et al (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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  118. Bloom K, Ely A, Mussolino C et al (2013) Inactivation of hepatitis B virus replication in cultured cells and in vivo with engineered transcription activator-like effector nucleases. Mol Ther 21(10):1889–1897

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  119. Chen J, Zhang W, Lin J et al (2014) An efficient antiviral strategy for targeting hepatitis B virus genome using transcription activator-like effector nucleases. Mol Ther 22(2):303–311

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  120. Xu L, Zhao P, Mariano A et al (2013) Targeted myostatin gene editing in multiple mammalian species directed by a single pair of TALE nucleases. Mol Ther Nucleic Acids 2:e112

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  121. Guilinger JP, Pattanayak V, Reyon D et al (2014) Broad specificity profiling of TALENs results in engineered nucleases with improved DNA-cleavage specificity. Nat Methods 11(4):429–435

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  122. Maeder ML, Linder SJ, Reyon D et al (2013) Robust, synergistic regulation of human gene expression using TALE activators. Nat Methods 10(3):243–245

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  123. Mali P, Esvelt KM, Church GM (2013) Cas9 as a versatile tool for engineering biology. Nat Methods 10(10):957–963

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  124. Hsu PD, Lander ES, Zhang F (2014) Development and applications of CRISPR-Cas9 for genome engineering. Cell 157(6):1262–1278

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  125. Sung YH, Baek IJ, Kim DH et al (2013) Knockout mice created by TALEN-mediated gene targeting. Nat Biotechnol 31(1):23–24

    Article  CAS  PubMed  Google Scholar 

  126. Zu Y, Tong X, Wang Z et al (2013) TALEN-mediated precise genome modification by homologous recombination in zebrafish. Nat Methods 10(4):329–331

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by a US National Institutes of Health (NIH) Director’s New Innovator Award (DP2OD008586), National Science Foundation (NSF) Faculty Early Career Development (CAREER) Award (CBET-1151035), NIH R01DA036865, NIH R21AR065956, NIH UH3TR000505, NIH P30AR066527, the Duke Coulter Translational Partnership, and an American Heart Association Scientist Development Grant (10SDG3060033). D.G.O. was supported by an American Heart Association Mid-Atlantic Affiliate Predoctoral Fellowship.

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Correspondence to Charles A. Gersbach Ph.D. .

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Ousterout, D.G., Gersbach, C.A. (2016). The Development of TALE Nucleases for Biotechnology. In: Kühn, R., Wurst, W., Wefers, B. (eds) TALENs. Methods in Molecular Biology, vol 1338. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2932-0_3

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  • DOI: https://doi.org/10.1007/978-1-4939-2932-0_3

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  • Online ISBN: 978-1-4939-2932-0

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