Skip to main content

Advertisement

SpringerLink
Log in

Molecular scissors and their application in genetically modified farm animals

  • Review
  • Published:
Transgenic Research Aims and scope Submit manuscript

Abstract

Molecular scissors (MS), incl. Zinc Finger Nucleases (ZFN), Transcription-activator like endoncleases (TALENS) and meganucleases possess long recognition sites and are thus capable of cutting DNA in a very specific manner. These molecular scissors mediate targeted genetic alterations by enhancing the DNA mutation rate via induction of double-strand breaks at a predetermined genomic site. Compared to conventional homologous recombination based gene targeting, MS can increase the targeting rate 10,000-fold, and gene disruption via mutagenic DNA repair is stimulated at a similar frequency. The successful application of different MS has been shown in different organisms, including insects, amphibians, plants, nematodes, and mammals, including humans. Recently, another novel class of molecular scissors was described that uses RNAs to target a specific genomic site. The CRISPR/Cas9 system is capable of targeting even multiple genomic sites in one shot and thus could be superior to ZFNs or TALEN, especially by its easy design. MS can be successfully employed for improving the understanding of complex physiological systems, producing transgenic animals, incl. creating large animal models for human diseases, creating specific cell lines, and plants, and even for treating human genetic diseases. This review provides an update on molecular scissors, their underlying mechanism and focuses on new opportunities for generating genetically modified farm animals.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Arnould S, Chames P, Perez C, Lacroix E, Duclert A, Epinat JC, Stricher F, Petit AS, Patin A, Guillier S, Rolland S, Prieto J, Blanco FJ, Bravo J, Montoya G, Serrano L, Duchateau P, Paques F (2006) Engineering of large numbers of highly specific homing endonucleases that induce recombination on novel DNA targets. J Mol Biol 355(3):443–458. doi:10.1016/j.jmb.2005.10.065

    Article  CAS  PubMed  Google Scholar 

  • Arnould S, Delenda C, Grizot S, Desseaux C, Paques F, Silva GH, Smith J (2011) The I-CreI meganuclease and its engineered derivatives: applications from cell modification to gene therapy. Protein Eng Des Sel PEDS 24(1–2):27–31. doi:10.1093/protein/gzq083

    Article  CAS  Google Scholar 

  • Bhaya D, Davison M, Barrangou R (2011) CRISPR-Cas systems in bacteria and archaea: versatile small RNAs for adaptive defense and regulation. Annu Rev Genet 45:273–297. doi:10.1146/annurev-genet-110410-132430

    Article  CAS  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(3):1169–1175

    PubMed Central  CAS  PubMed  Google Scholar 

  • Boch J, Bonas U (2010) Xanthomonas AvrBs3 family-type III effectors: discovery and function. Annu Rev Phytopathol 48:419–436. doi:10.1146/annurev-phyto-080508-081936

    Article  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(5959):1509–1512. doi:10.1126/science.1178811

    Article  CAS  PubMed  Google Scholar 

  • Carbery ID, Ji D, Harrington A, Brown V, Weinstein EJ, Liaw L, Cui X (2010) Targeted genome modification in mice using zinc-finger nucleases. Genetics 186(2):451–459. doi:10.1534/genetics.110.117002

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Carlson DF, Tan W, Lillico SG, Stverakova D, Proudfoot C, Christian M, Voytas DF, Long CR, Whitelaw CB, Fahrenkrug SC (2012) Efficient TALEN-mediated gene knockout in livestock. Proc Natl Acad Sci USA 109(43):17382–17387. doi:10.1073/pnas.1211446109

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cathomen T, Joung JK (2008) Zinc-finger nucleases: the next generation emerges. Mol Ther 16(7):1200–1207. doi:10.1038/mt.2008.114

    Article  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(12):e82. doi:10.1093/nar/gkr218

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chevalier BS, Stoddard BL (2001) Homing endonucleases: structural and functional insight into the catalysts of intron/intein mobility. Nucleic Acids Res 29(18):3757–3774

    Article  PubMed Central  CAS  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(4):1968–1973

    PubMed Central  CAS  PubMed  Google Scholar 

  • Christian M, Cermak T, Doyle E, Schmidt C, Zhang F, Hummel A, Bogdanove A, Voytas D (2010) Targeting DNA double-strand breaks with TAL effector nucleases. Genetics 186(2):757–761

    Article  PubMed Central  CAS  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(6121):819–823. doi:10.1126/science.1231143

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cooper DK, Ayares D (2011) The immense potential of xenotransplantation in surgery. Int J Surg 9(2):122–129. doi:10.1016/j.ijsu.2010.11.002

    Article  PubMed  Google Scholar 

  • Cui X, Ji D, Fisher DA, Wu Y, Briner DM, Weinstein EJ (2011) Targeted integration in rat and mouse embryos with zinc-finger nucleases. Nat Biotechnol 29(1):64–67. doi:10.1038/nbt.1731

    Article  CAS  PubMed  Google Scholar 

  • De P, Rodgers KK (2004) Putting the pieces together: identification and characterization of structural domains in the V(D)J recombination protein RAG1. Immunol Rev 200:70–82. doi:10.1111/j.0105-2896.2004.00154.x

    Article  CAS  PubMed  Google Scholar 

  • de Villartay JP, Fischer A, Durandy A (2003) The mechanisms of immune diversification and their disorders. Nat Rev Immunol 3(12):962–972. doi:10.1038/nri1247

    Article  PubMed  CAS  Google Scholar 

  • Defrancesco L (2011) Move over ZFNs. Nat Biotechnol 29(8):681–684

    Article  CAS  Google Scholar 

  • Deng C, Capecchi MR (1992) Reexamination of gene targeting frequency as a function of the extent of homology between the targeting vector and the target locus. Mol Cell Biol 12(8):3365–3371

    PubMed Central  CAS  PubMed  Google Scholar 

  • Donoho G, Jasin M, Berg P (1998) Analysis of gene targeting and intrachromosomal homologous recombination stimulated by genomic double-strand breaks in mouse embryonic stem cells. Mol Cell Biol 18(7):4070–4078

    PubMed Central  CAS  PubMed  Google Scholar 

  • Doyon JB, Pattanayak V, Meyer CB, Liu DR (2006) Directed evolution and substrate specificity profile of homing endonuclease I-SceI. J Am Chem Soc 128(7):2477–2484. doi:10.1021/ja057519l

    Article  CAS  PubMed  Google Scholar 

  • Doyon Y, McCammon JM, Miller JC, Faraji F, Ngo C, Katibah GE, Amora R, Hocking TD, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Amacher SL (2008) Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases. Nat Biotechnol 26(6):702–708. doi:10.1038/nbt1409

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Doyon Y, Choi VM, Xia DF, Vo TD, Gregory PD, Holmes MC (2010) Transient cold shock enhances zinc-finger nuclease-mediated gene disruption. Nat Methods 7(6):459–460

    Article  CAS  PubMed  Google Scholar 

  • Epinat JC, Arnould S, Chames P, Rochaix P, Desfontaines D, Puzin C, Patin A, Zanghellini A, Paques F, Lacroix E (2003) A novel engineered meganuclease induces homologous recombination in yeast and mammalian cells. Nucleic Acids Res 31(11):2952–2962

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Flannagan RS, Linn T, Valvano MA (2008) A system for the construction of targeted unmarked gene deletions in the genus Burkholderia. Environ Microbiol 10(6):1652–1660. doi:10.1111/j.1462-2920.2008.01576.x

    Article  CAS  PubMed  Google Scholar 

  • Flisikowska T, Thorey IS, Offner S, Ros F, Lifke V, Zeitler B, Rottmann O, Vincent A, Zhang L, Jenkins S, Niersbach H, Kind AJ, Gregory PD, Schnieke AE, Platzer J (2011) Efficient immunoglobulin gene disruption and targeted replacement in rabbit using zinc finger nucleases. PLoS ONE 6(6):e21045. doi:10.1371/journal.pone.0021045

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Flisikowska T, Merkl C, Landmann M, Eser S, Rezaei N, Cui X, Kurome M, Zakhartchenko V, Kessler B, Wieland H, Rottmann O, Schmid RM, Schneider G, Kind A, Wolf E, Saur D, Schnieke A (2012) A porcine model of familial adenomatous polyposis. Gastroenterology 143(5):1173–1175. doi:10.1053/j.gastro.2012.07.110

    Article  CAS  PubMed  Google Scholar 

  • Flisikowska T, Kind A, Schnieke A (2014) Genetically modified pigs to model human diseases. J Appl Genet 55(1):53–64. doi:10.1007/s13353-013-0182-9

    Article  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(3):279–284. doi:10.1038/nbt.2808

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Geurts AM, Cost GJ, Freyvert Y, Zeitler B, Miller JC, Choi VM, Jenkins SS, Wood A, Cui X, Meng X, Vincent A, Lam S, Michalkiewicz M, Schilling R, Foeckler J, Kalloway S, Weiler H, Menoret S, Anegon I, Davis GD, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Jacob HJ, Buelow R (2009) Knockout rats via embryo microinjection of zinc-finger nucleases. Science 325(5939):433. doi:10.1126/science.1172447

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Grabher C, Wittbrodt J (2008) Recent advances in meganuclease-and transposon-mediated transgenesis of medaka and zebrafish. Methods Mol Biol (Clifton, NJ) 461:521–539. doi:10.1007/978-1-60327-483-8_36

    Article  CAS  Google Scholar 

  • Grizot S, Smith J, Daboussi F, Prieto J, Redondo P, Merino N, Villate M, Thomas S, Lemaire L, Montoya G, Blanco FJ, Paques F, Duchateau P (2009) Efficient targeting of a SCID gene by an engineered single-chain homing endonuclease. Nucleic Acids Res 37(16):5405–5419. doi:10.1093/nar/gkp548

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Guilinger JP, Thompson DB, Liu DR (2014) Fusion of catalytically inactive Cas9 to FokI nuclease improves the specificity of genome modification. Nat Biotechnol. doi:10.1038/nbt.2909

    PubMed Central  Google Scholar 

  • Hai T, Teng F, Guo R, Li W, Zhou Q (2014) One-step generation of knockout pigs by zygote injection of CRISPR/Cas system. Cell Res 24(3):372–375. doi:10.1038/cr.2014.11

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hauschild J, Petersen B, Santiago Y, Queisser AL, Carnwath JW, Lucas-Hahn A, Zhang L, Meng X, Gregory PD, Schwinzer R, Cost GJ, Niemann H (2011) Efficient generation of a biallelic knockout in pigs using zinc-finger nucleases. Proc Natl Acad Sci USA 108(29):12013–12017. doi:10.1073/pnas.1106422108

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hauschild-Quintern J, Petersen B, Cost GJ, Niemann H (2013a) Gene knockout and knockin by zinc-finger nucleases: current status and perspectives. Cell Mol Life Sci 70(16):2969–2983. doi:10.1007/s00018-012-1204-1

    Article  CAS  PubMed  Google Scholar 

  • Hauschild-Quintern J, Petersen B, Queisser AL, Lucas-Hahn A, Schwinzer R, Niemann H (2013b) Gender non-specific efficacy of ZFN mediated gene targeting in pigs. Transgenic Res 22(1):1–3. doi:10.1007/s11248-012-9647-6

    Article  CAS  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(8):731–734. doi:10.1038/nbt.1927

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Horzempa J, Shanks RM, Brown MJ, Russo BC, O’Dee DM, Nau GJ (2010) Utilization of an unstable plasmid and the I-SceI endonuclease to generate routine markerless deletion mutants in Francisella tularensis. J Microbiol Methods 80(1):106–108. doi:10.1016/j.mimet.2009.10.013

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Huang P, Xiao A, Zhou M, Zhu Z, Lin S, Zhang B (2011) Heritable gene targeting in zebrafish using customized TALENs. Nat Biotechnol 29(8):699–700. doi:10.1038/nbt.1939

    Article  PubMed  CAS  Google Scholar 

  • Jacquier A, Dujon B (1985) An intron-encoded protein is active in a gene conversion process that spreads an intron into a mitochondrial gene. Cell 41(2):383–394

    Article  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. doi:10.7554/eLife.00471

    Article  PubMed Central  PubMed  Google Scholar 

  • Kim YG, Cha J, Chandrasegaran S (1996) Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. Proc Natl Acad Sci USA 93(3):1156–1160

    Article  PubMed Central  CAS  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 JS (2013) A library of TAL effector nucleases spanning the human genome. Nat Biotechnol 31(3):251–258. doi:10.1038/nbt.2517

    Article  CAS  PubMed  Google Scholar 

  • Kurome M, Geistlinger L, Kessler B, Zakhartchenko V, Klymiuk N, Wuensch A, Richter A, Baehr A, Kraehe K, Burkhardt K, Flisikowski K, Flisikowska T, Merkl C, Landmann M, Durkovic M, Tschukes A, Kraner S, Schindelhauer D, Petri T, Kind A, Nagashima H, Schnieke A, Zimmer R, Wolf E (2013) Factors influencing the efficiency of generating genetically engineered pigs by nuclear transfer: multi-factorial analysis of a large data set. BMC Biotechnol 13:43. doi:10.1186/1472-6750-13-43

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Li T, Huang S, Jiang WZ, Wright D, Spalding MH, Weeks DP, Yang B (2011a) TAL nucleases (TALNs): hybrid proteins composed of TAL effectors and FokI DNA-cleavage domain. Nucleic Acids Res 39(1):359–372. doi:10.1093/nar/gkq704

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Li T, Huang S, Zhao X, Wright DA, Carpenter S, Spalding MH, Weeks DP, Yang B (2011b) Modularly assembled designer TAL effector nucleases for targeted gene knockout and gene replacement in eukaryotes. Nucleic Acids Res 39(14):6315–6325. doi:10.1093/nar/gkr188

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Li P, Estrada JL, Burlak C, Montgomery J, Butler JR, Santos RM, Wang ZY, Paris LL, Blankenship RL, Downey SM, Tector M, Tector AJ (2014) Efficient generation of genetically distinct pigs in a single pregnancy using multiplexed single-guide RNA and carbohydrate selection. Xenotransplantation. doi:10.1111/xen.12131

    Google Scholar 

  • Lillico SG, Proudfoot C, Carlson DF, Stverakova D, Neil C, Blain C, King TJ, Ritchie WA, Tan W, Mileham AJ, McLaren DG, Fahrenkrug SC, Whitelaw CB (2013) Live pigs produced from genome edited zygotes. Sci Rep 3:2847. doi:10.1038/srep02847

    Article  PubMed  Google Scholar 

  • Liu X, Wang Y, Guo W, Chang B, Liu J, Guo Z, Quan F, Zhang Y (2013) Zinc-finger nickase-mediated insertion of the lysostaphin gene into the beta-casein locus in cloned cows. Nat Commun 4:2565. doi:10.1038/ncomms3565

    PubMed Central  PubMed  Google Scholar 

  • Loeber J, Pan FC, Pieler T (2009) Generation of transgenic frogs. Methods Mol Biol (Clifton NJ 561:65–72. doi:10.1007/978-1-60327-019-9_4

    Article  CAS  Google Scholar 

  • Luo Y, Bolund L, Sorensen CB (2012) Pig gene knockout by rAAV-mediated homologous recombination: comparison of BRCA1 gene knockout efficiency in Yucatan and Gottingen fibroblasts with slightly different target sequences. Transgenic Res 21(3):671–676. doi:10.1007/s11248-011-9563-1

    Article  CAS  PubMed  Google Scholar 

  • Maggert KA, Gong WJ, Golic KG (2008) Methods for homologous recombination in Drosophila. Methods Mol Biol (Clifton NJ) 420:155–174. doi:10.1007/978-1-59745-583-1_9

    Article  CAS  Google Scholar 

  • Mahfouz MM, Li L, Shamimuzzaman M, Wibowo A, Fang X, Zhu JK (2011) De novo-engineered transcription activator-like effector (TALE) hybrid nuclease with novel DNA binding specificity creates double-strand breaks. Proc Natl Acad Sci USA 108(6):2623–2628. doi:10.1073/pnas.1019533108

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Meng X, Noyes MB, Zhu LJ, Lawson ND, Wolfe SA (2008) Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases. Nat Biotechnol 26(6):695–701. doi:10.1038/nbt1398

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Menoret S, Fontaniere S, Jantz D, Tesson L, Thinard R, Remy S, Usal C, Ouisse LH, Fraichard A, Anegon I (2013) Generation of Rag1-knockout immunodeficient rats and mice using engineered meganucleases. FASEB J 27(2):703–711. doi:10.1096/fj.12-219907

    Article  CAS  PubMed  Google Scholar 

  • Meselson MS, Radding CM (1975) A general model for genetic recombination. Proc Natl Acad Sci USA 72(1):358–361

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Meyer M, de Angelis MH, Wurst W, Kuhn R (2010) Gene targeting by homologous recombination in mouse zygotes mediated by zinc-finger nucleases. Proc Natl Acad Sci USA 107(34):15022–15026. doi:10.1073/pnas.1009424107

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mikkelsen M, Moller A, Jensen LH, Pedersen A, Harajehi JB, Pakkenberg H (1999) MPTP-induced Parkinsonism in minipigs: a behavioral, biochemical, and histological study. Neurotoxicol Teratol 21(2):169–175

    Article  CAS  PubMed  Google Scholar 

  • Miller J, McLachlan AD, Klug A (1985) Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes. EMBO J 4(6):1609–1614

    PubMed Central  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(2):143–148. doi:10.1038/nbt.1755

    Article  CAS  PubMed  Google Scholar 

  • Moehle EA, Rock JM, Lee YL, Jouvenot Y, DeKelver RC, Gregory PD, Urnov FD, Holmes MC (2007) Targeted gene addition into a specified location in the human genome using designed zinc finger nucleases. Proc Natl Acad Sci USA 104(9):3055–3060. doi:10.1073/pnas.0611478104

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Moscou MJ, Bogdanove AJ (2009) A simple cipher governs DNA recognition by TAL effectors. Science 326(5959):1501. doi:10.1126/science.1178817

    Article  CAS  PubMed  Google Scholar 

  • Orlando SJ, Santiago Y, DeKelver RC, Freyvert Y, Boydston EA, Moehle EA, Choi VM, Gopalan SM, Lou JF, Li J, Miller JC, Holmes MC, Gregory PD, Urnov FD, Cost GJ (2010) Zinc-finger nuclease-driven targeted integration into mammalian genomes using donors with limited chromosomal homology. Nucleic Acids Res 38(15):e152. doi:10.1093/nar/gkq512

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Orlowski J, Boniecki M, Bujnicki JM (2007) I-Ssp6803I: the first homing endonuclease from the PD-(D/E)XK superfamily exhibits an unusual mode of DNA recognition. Bioinformatics 23(5):527–530. doi:10.1093/bioinformatics/btm007

    Article  CAS  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. doi:10.1146/annurev.biochem.70.1.313

    Article  CAS  PubMed  Google Scholar 

  • Palgrave CJ, Gilmour L, Lowden CS, Lillico SG, Mellencamp MA, Whitelaw CB (2011) Species-specific variation in RELA underlies differences in NF-κB activity: a potential role in African swine fever pathogenesis. J Virol 85(12):6008–6014. doi:10.1128/JVI.00331-11

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pavletich NP, Pabo CO (1991) Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A. Science 252(5007):809–817

    Article  CAS  PubMed  Google Scholar 

  • Petersen B, Lucas-Hahn A, Oropeza M, Hornen N, Lemme E, Hassel P, Queisser AL, Niemann H (2008) Development and validation of a highly efficient protocol of porcine somatic cloning using preovulatory embryo transfer in peripubertal gilts. Cloning Stem Cells 10(3):355–362. doi:10.1089/clo.2008.0026

    Article  CAS  PubMed  Google Scholar 

  • Posfai G, Kolisnychenko V, Bereczki Z, Blattner FR (1999) Markerless gene replacement in Escherichia coli stimulated by a double-strand break in the chromosome. Nucleic Acids Res 27(22):4409–4415

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Proudfoot C, Carlson DF, Huddart R, Long CR, Pryor JH, King TJ, Lillico SG, Mileham AJ, McLaren DG, Whitelaw CB, Fahrenkrug SC (2015) Genome edited sheep and cattle. Transgenic Res 24(1):147–153. doi:10.1007/s11248-014-9832-x

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Puchta H (1999) Use of I-Sce I to induce DNA double-strand breaks in Nicotiana. Methods Mol Biol (Clifton, NJ) 113:447–451. doi:10.1385/1-59259-675-4:447

    CAS  Google Scholar 

  • Puchta H (2002) Gene replacement by homologous recombination in plants. Plant Mol Biol 48(1–2):173–182

    Article  CAS  PubMed  Google Scholar 

  • Radding CM (1982) Homologous pairing and strand exchange in genetic recombination. Annu Rev Genet 16:405–437. doi:10.1146/annurev.ge.16.120182.002201

    Article  CAS  PubMed  Google Scholar 

  • Renfer E, Amon-Hassenzahl A, Steinmetz PR, Technau U (2010) A muscle-specific transgenic reporter line of the sea anemone, Nematostella vectensis. Proc Natl Acad Sci USA 107(1):104–108. doi:10.1073/pnas.0909148107

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rogers CS, Stoltz DA, Meyerholz DK, Ostedgaard LS, Rokhlina T, Taft PJ, Rogan MP, Pezzulo AA, Karp PH, Itani OA, Kabel AC, Wohlford-Lenane CL, Davis GJ, Hanfland RA, Smith TL, Samuel M, Wax D, Murphy CN, Rieke A, Whitworth K, Uc A, Starner TD, Brogden KA, Shilyansky J, McCray PB Jr, Zabner J, Prather RS, Welsh MJ (2008) Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs. Science 321(5897):1837–1841. doi:10.1126/science.1163600

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rosen LE, Morrison HA, Masri S, Brown MJ, Springstubb B, Sussman D, Stoddard BL, Seligman LM (2006) Homing endonuclease I-CreI derivatives with novel DNA target specificities. Nucleic Acids Res 34(17):4791–4800. doi:10.1093/nar/gkl645

    Article  PubMed Central  CAS  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 USA 91(13):6064–6068

    Article  PubMed Central  CAS  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(12):8096–8106

    PubMed Central  CAS  PubMed  Google Scholar 

  • Sander JD, Cade L, Khayter C, Reyon D, Peterson RT, Joung JK, Yeh JR (2011) Targeted gene disruption in somatic zebrafish cells using engineered TALENs. Nat Biotechnol 29(8):697–698. doi:10.1038/nbt.1934

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Seligman LM, Chisholm KM, Chevalier BS, Chadsey MS, Edwards ST, Savage JH, Veillet AL (2002) Mutations altering the cleavage specificity of a homing endonuclease. Nucleic Acids Res 30(17):3870–3879

    Article  PubMed Central  CAS  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(4):399–402. doi:10.1038/nmeth.2857

    Article  CAS  PubMed  Google Scholar 

  • Siebert R, Puchta H (2002) Efficient repair of genomic double-strand breaks by homologous recombination between directly repeated sequences in the plant genome. Plant Cell 14(5):1121–1131

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Silva G, Poirot L, Galetto R, Smith J, Montoya G, Duchateau P, Paques F (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 

  • Smih F, Rouet P, Romanienko PJ, Jasin M (1995) Double-strand breaks at the target locus stimulate gene targeting in embryonic stem cells. Nucleic Acids Res 23(24):5012–5019

    Article  PubMed Central  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(17):3361–3369

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Smith J, Grizot S, Arnould S, Duclert A, Epinat JC, Chames P, Prieto J, Redondo P, Blanco FJ, Bravo J, Montoya G, Paques F, Duchateau P (2006) A combinatorial approach to create artificial homing endonucleases cleaving chosen sequences. Nucleic Acids Res 34(22):e149. doi:10.1093/nar/gkl720

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Sussman D, Chadsey M, Fauce S, Engel A, Bruett A, Monnat R Jr, Stoddard BL, Seligman LM (2004) Isolation and characterization of new homing endonuclease specificities at individual target site positions. J Mol Biol 342(1):31–41. doi:10.1016/j.jmb.2004.07.031

    Article  CAS  PubMed  Google Scholar 

  • Szczepek M, Brondani V, Buchel J, Serrano L, Segal DJ, Cathomen T (2007) Structure-based redesign of the dimerization interface reduces the toxicity of zinc-finger nucleases. Nat Biotechnol 25(7):786–793. doi:10.1038/nbt1317

    Article  CAS  PubMed  Google Scholar 

  • Takeuchi H, Georgiev O, Fetchko M, Kappeler M, Schaffner W, Egli D (2007) In vivo construction of transgenes in Drosophila. Genetics 175(4):2019–2028. doi:10.1534/genetics.106.065920

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tan W, Carlson DF, Lancto CA, Garbe JR, Webster DA, Hackett PB, Fahrenkrug SC (2013) Efficient nonmeiotic allele introgression in livestock using custom endonucleases. Proc Natl Acad Sci USA 110(41):16526–16531. doi:10.1073/pnas.1310478110

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Terns MP, Terns RM (2011) CRISPR-based adaptive immune systems. Curr Opin Microbiol 14(3):321–327. doi:10.1016/j.mib.2011.03.005

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tesson L, Usal C, Menoret S, Leung E, Niles BJ, Remy S, Santiago Y, Vincent AI, Meng X, Zhang L, Gregory PD, Anegon I, Cost GJ (2011) Knockout rats generated by embryo microinjection of TALENs. Nat Biotechnol 29(8):695–696. doi:10.1038/nbt.1940

    Article  CAS  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(6):569–576. doi:10.1038/nbt.2908

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Urnov FD, Miller JC, Lee YL, 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(7042):646–651. doi:10.1038/nature03556

    Article  CAS  PubMed  Google Scholar 

  • van den Heuvel M, Sorop O, Koopmans SJ, Dekker R, de Vries R, van Beusekom HM, Eringa EC, Duncker DJ, Danser AH, van der Giessen WJ (2012) Coronary microvascular dysfunction in a porcine model of early atherosclerosis and diabetes. Am J Physiol Heart Circ Physiol 302(1):H85–H94. doi:10.1152/ajpheart.00311.2011

    Article  PubMed  CAS  Google Scholar 

  • Vasquez KM, Marburger K, Intody Z, Wilson JH (2001) Manipulating the mammalian genome by homologous recombination. Proc Natl Acad Sci USA 98(15):8403–8410. doi:10.1073/pnas.111009698

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Voytas DF, Joung JK (2009) Plant science. DNA binding made easy. Science 326(5959):1491–1492. doi:10.1126/science.1183604

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Friedman G, Doyon Y, Wang NS, Li CJ, Miller JC, Hua KL, Yan JJ, Babiarz JE, Gregory PD, Holmes MC (2012) Targeted gene addition to a predetermined site in the human genome using a ZFN-based nicking enzyme. Genome Res 22(7):1316–1326. doi:10.1101/gr.122879.111

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Wang H, Yang H, Shivalila CS, Dawlaty MM, Cheng AW, Zhang F, Jaenisch R (2013) One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell 153(4):910–918. doi:10.1016/j.cell.2013.04.025

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Watanabe M, Umeyama K, Matsunari H, Takayanagi S, Haruyama E, Nakano K, Fujiwara T, Ikezawa Y, Nakauchi H, Nagashima H (2010) Knockout of exogenous EGFP gene in porcine somatic cells using zinc-finger nucleases. Biochem Biophys Res Commun 402(1):14–18

    Article  CAS  PubMed  Google Scholar 

  • Watanabe M, Nakano K, Matsunari H, Matsuda T, Maehara M, Kanai T, Kobayashi M, Matsumura Y, Sakai R, Kuramoto M, Hayashida G, Asano Y, Takayanagi S, Arai Y, Umeyama K, Nagaya M, Hanazono Y, Nagashima H (2013) Generation of interleukin-2 receptor gamma gene knockout pigs from somatic cells genetically modified by zinc finger nuclease-encoding mRNA. PLoS ONE 8(10):e76478. doi:10.1371/journal.pone.0076478

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Whitworth KM, Lee K, Benne JA, Beaton BP, Spate LD, Murphy SL, Samuel MS, Mao J, O’Gorman C, Walters EM, Murphy CN, Driver J, Mileham A, McLaren D, Wells KD, Prather RS (2014a) Use of the CRISPR/Cas9 system to produce genetically engineered pigs from in vitro-derived oocytes and embryos. Biol Reprod 91(3):78. doi:10.1095/biolreprod.114.121723

    Article  PubMed  CAS  Google Scholar 

  • Whitworth KM, Lee K, Benne JA, Beaton BP, Spate LD, Murphy SL, Samuel MS, Mao J, O’Gorman C, Walters EM, Murphy CN, Driver JP, Mileham A, McLaren D, Wells KD, Prather RS (2014b) Use of the CRISPR/Cas9 system to produce genetically engineered pigs from in vitro-derived oocytes and embryos. Biol Reprod. doi:10.1095/biolreprod.114.121723

    PubMed  Google Scholar 

  • Whyte JJ, Prather RS (2011) Zinc finger nucleases to create custom-designed modifications in the swine (Sus scrofa) genome. J Anim Sci. doi:10.2527/jas.2011-4546

    PubMed  Google Scholar 

  • Whyte JJ, Zhao J, Wells KD, Samuel MS, Whitworth KM, Walters EM, Laughlin MH, Prather RS (2011) Gene targeting with zinc finger nucleases to produce cloned eGFP knockout pigs. Mol Reprod Dev 78(1):2. doi:10.1002/mrd.21271

    Article  CAS  PubMed  Google Scholar 

  • Wiedenheft B, Sternberg SH, Doudna JA (2012) RNA-guided genetic silencing systems in bacteria and archaea. Nature 482(7385):331–338. doi:10.1038/nature10886

    Article  CAS  PubMed  Google Scholar 

  • Windbichler N, Papathanos PA, Catteruccia F, Ranson H, Burt A, Crisanti A (2007) Homing endonuclease mediated gene targeting in Anopheles gambiae cells and embryos. Nucleic Acids Res 35(17):5922–5933. doi:10.1093/nar/gkm632

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yang D, Yang H, Li W, Zhao B, Ouyang Z, Liu Z, Zhao Y, Fan N, Song J, Tian J, Li F, Zhang J, Chang L, Pei D, Chen YE, Lai L (2011) Generation of PPARgamma mono-allelic knockout pigs via zinc-finger nucleases and nuclear transfer cloning. Cell Res. doi:10.1038/cr.2011.70

    Google Scholar 

  • Yang H, Wang H, Shivalila CS, Cheng AW, Shi L, Jaenisch R (2013) One-step generation of mice carrying reporter and conditional alleles by CRISPR/Cas-mediated genome engineering. Cell 154(6):1370–1379. doi:10.1016/j.cell.2013.08.022

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yu BJ, Kang KH, Lee JH, Sung BH, Kim MS, Kim SC (2008) Rapid and efficient construction of markerless deletions in the Escherichia coli genome. Nucleic Acids Res 36(14):e84. doi:10.1093/nar/gkn359

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Yu S, Luo J, Song Z, Ding F, Dai Y, Li N (2011) Highly efficient modification of beta-lactoglobulin (BLG) gene via zinc-finger nucleases in cattle. Cell Res 21(11):1638–1640. doi:10.1038/cr.2011.153

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut, Hoeltystrasse 10, 31535, Neustadt, Mariensee, Germany

    Bjoern Petersen & Heiner Niemann

  2. Rebirth, Cluster of Excellence, Hannover Medical School, Hannover, Germany

    Bjoern Petersen & Heiner Niemann

Authors
  1. Bjoern Petersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Heiner Niemann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Bjoern Petersen or Heiner Niemann.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Petersen, B., Niemann, H. Molecular scissors and their application in genetically modified farm animals. Transgenic Res 24, 381–396 (2015). https://doi.org/10.1007/s11248-015-9862-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11248-015-9862-z

Keywords

Search

Navigation