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Evolution of Transgenic Technology: From Random Transgenesis to Precise Genome Editing

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Sustainable Agriculture Reviews

Part of the book series: Sustainable Agriculture Reviews ((SARV,volume 62))

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Abstract

New techniques in molecular biology help us for better understanding of biological processes. As biologists we resort to powerful approaches for efficient gene transfer which would enable us to study alterations in gene activity, in vivo. Although embryonic stem cell mediated transgenesis enabled targeted gene transfer through homologous recombination, the efficiency of such techniques remains very low. The recent emergence of genome editing technology provides a feasible approach to introduce a variety of precise heritable modifications into the mammalian genome. In this chapter, we review conventional transgenic methods, the transgene design and the structure and function of different genome editors. Further, we provide updates on the diverse applications of genome editing technology pertaining to agriculture and biomedical research, and lastly discusses perspectives. Though the pronuclear injection method and embryonic stem cell technique were quite successful in generating transgenic mice, they remained highly challenging for livestock transgenesis.

The discovery of the somatic cell nuclear transfer (SCNT) technique led to fruitful development of transgenic farm animals, but suffers from low in utero survival rate. With the advent of genome editors, animal transgenesis gained new heights, a variety of precise modifications including multiplex gene edits and single base change could be performed with an unprecedented ease. Among all gene editors, CRISPR/Cas system has become the method of choice due to simplicity of construction, low cost and multiple gene editing ability. The diverse applications of gene editing technologies for generation of transgenic animal includes enhancing important production traits, improving disease resistance and developing animal bioreactors and biomedical models. Nevertheless, there are many hurdles yet to be resolved, development of improved genome editing tools would necessarily ensure bright application in the field of animal transgenesis.

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Abbreviations

3′ UTR:

3′ untranslated region

5′ UTR:

5′ untranslated region

CRISPR:

Clustered Regularly Interspaced Short Palindromic Repeat

DNA:

Deoxyribonucleic acid

ESC:

Embryonic stem cell

HDR:

Homology Directed Repair

NHEJ:

Non-Homologous End Joining

RNA:

Ribonucleic acid

SCNT:

Somatic Cell Nuclear Transfer

TALEN:

Transcription Activator-Like Effector Nuclease

ZFN:

Zinc finger nuclease

crRNA:

CRISPR RNA

References

  • Adams D, Baldock R, Bhattacharya S et al (2013) Bloomsbury report on mouse embryo phenotyping: recommendations from the IMPC workshop on embryonic lethal screening. Dis Model Mech 6:571–579

    Article  PubMed  PubMed Central  Google Scholar 

  • Baldassarre H, Keefer C, Wang B et al (2003) Nuclear transfer in goats using in vitro matured oocytes recovered by laparoscopic ovum pick-up. Cloning Stem Cells 5:279–285

    Article  CAS  PubMed  Google Scholar 

  • Barrangou R, Fremaux C, Deveau H et al (2007) CRISPR provides acquired resistance against viruses in prokaryotes. Science 315:1709–1712

    Article  CAS  PubMed  Google Scholar 

  • Bi Y, Hua Z, Liu X et al (2016) Isozygous and selectable marker-free MSTN knockout cloned pigs generated by the combined use of CRISPR/Cas9 and Cre/LoxP. Sci Rep 6:1–12

    Article  Google Scholar 

  • Bouuaert CC, Chalmers RM (2010) Gene therapy vectors: the prospects and potentials of the cut-and-paste transposons. Genetica 138:473–484

    Article  Google Scholar 

  • Brinster RL, Chen HY, Trumbauer M et al (1981) Somatic expression of herpes thymidine kinase in mice following injection of a fusion gene into eggs. Cell 27:223–231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Campbell KH, McWhir J, Ritchie WA, Wilmut I (1996) Sheep cloned by nuclear transfer from a cultured cell line. Nature 380:64–66

    Article  CAS  PubMed  Google Scholar 

  • Canalis E, Yu J, Schilling L et al (2018) The lateral meningocele syndrome mutation causes marked osteopenia in mice. J Biol Chem 293:14165–14177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Capecchi MR (1989) Altering the genome by homologous recombination. Science 244:1288–1292

    Article  CAS  PubMed  Google Scholar 

  • Capecchi MR (2005) Gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century. Nat Rev Genet 6:507–512

    Article  CAS  PubMed  Google Scholar 

  • Carbery ID, Ji D, Harrington A et al (2010) Targeted genome modification in mice using zinc-finger nucleases. Genetics 186:451–459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carlson DF, Lancto CA, Zang B et al (2016) Production of hornless dairy cattle from genome-edited cell lines. Nat Biotechnol 34:479–481

    Article  CAS  PubMed  Google Scholar 

  • Chen K, Gao C (2013) TALENs: customizable molecular DNA scissors for genome engineering of plants. J Genet Genomics 40:271–279

    Article  PubMed  Google Scholar 

  • Cho B, Kim SJ, Lee E-J et al (2018) Generation of insulin-deficient piglets by disrupting INS gene using CRISPR/Cas9 system. Transgenic Res 27:289–300

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ciccarelli M, Giassetti MI, Miao D et al (2020) Donor-derived spermatogenesis following stem cell transplantation in sterile NANOS2 knockout males. Proc Natl Acad Sci 117:24195–24204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Costantini F (2001) Transgenic animal. In: Brenner’s Encyclopedia of genetics, 2bd edn, pp 117–123

    Chapter  Google Scholar 

  • Crispo M, Vilarino M, dos Santos-Neto PC et al (2015) Embryo development, fetal growth and postnatal phenotype of eGFP lambs generated by lentiviral transgenesis. Transgenic Res 24:31–41

    Article  CAS  PubMed  Google Scholar 

  • Cui X, Ji D, Fisher DA et al (2011) Targeted integration in rat and mouse embryos with zinc-finger nucleases. Nat Biotechnol 29:64–67

    Article  CAS  PubMed  Google Scholar 

  • Cui C, Song Y, Liu J et al (2015) Gene targeting by TALEN-induced homologous recombination in goats directs production of β-lactoglobulin-free, high-human lactoferrin milk. Sci Rep 5:1–11

    Google Scholar 

  • Dickinson DJ, Ward JD, Reiner DJ, Goldstein B (2013) Engineering the Caenorhabditis elegans genome using Cas9-triggered homologous recombination. Nat Methods 10:1028–1034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doudna JA, Charpentier E (2014) The new frontier of genome engineering with CRISPR-Cas9. Science 346:1258096

    Article  PubMed  Google Scholar 

  • Doyon Y, McCammon JM, Miller JC et al (2008) Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases. Nat Biotechnol 26:702–708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duan X, Liu J, Zheng X et al (2016) Deficiency of ATP6V1H causes bone loss by inhibiting bone resorption and bone formation through the TGF-β1 pathway. Theranostics 6:2183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fan Z, Perisse IV, Cotton CU et al (2018a) A sheep model of cystic fibrosis generated by CRISPR/Cas9 disruption of the CFTR gene. JCI Insight 3:e123529

    Article  PubMed  PubMed Central  Google Scholar 

  • Fan Z, Regouski M, Van Wettere AJ et al (2018b) 28 generation of immunoglobulin heavy constant mu (IGHM) knockout goats using CRISPR/Cas9 and somatic cell nuclear transfer. Reprod Fertil Dev 30:153–154

    Article  Google Scholar 

  • Fan Z, Yang M, Regouski M, Polejaeva IA (2019) Gene knockouts in goats using CRISPR/Cas9 system and somatic cell nuclear transfer. In: Microinjection. Springer, pp 373–390

    Chapter  Google Scholar 

  • Fang B, Ren X, Wang Y et al (2018) Apolipoprotein E deficiency accelerates atherosclerosis development in miniature pigs. Dis Model Mech 11:dmm036632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garton M, Najafabadi HS, Schmitges FW et al (2015) A structural approach reveals how neighbouring C2H2 zinc fingers influence DNA binding specificity. Nucleic Acids Res 43:9147–9157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geurts A, Balciunas D, Mates L (2011) Vertebrate transgenesis by transposition. In: Advanced protocols for animal transgenesis. Springer, pp 213–236

    Chapter  Google Scholar 

  • Giraldo P, Montoliu L (2001) Size matters: use of YACs, BACs and PACs in transgenic animals. Transgenic Res 10:83–103

    Article  CAS  PubMed  Google Scholar 

  • Giraldo P, Rival-Gervier S, Houdebine L-M, Montoliu L (2003) The potential benefits of insulators on heterologous constructs in transgenic animals. Transgenic Res 12:751–755

    Article  CAS  PubMed  Google Scholar 

  • Grabundzija I, Irgang M, Mátés L et al (2010) Comparative analysis of transposable element vector systems in human cells. Mol Ther 18:1200–1209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Graham C, Cole S, Laible G (2009) Site-specific modification of the bovine genome using Cre recombinase-mediated gene targeting. Biotechnol J Healthc Nutr Technol 4:108–118

    CAS  Google Scholar 

  • Gratz SJ, Cummings AM, Nguyen JN et al (2013) Genome engineering of Drosophila with the CRISPR RNA-guided Cas9 nuclease. Genetics 194:1029–1035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo R, Wan Y, Xu D et al (2016) Generation and evaluation of Myostatin knock-out rabbits and goats using CRISPR/Cas9 system. Sci Rep 6:1–10

    Google Scholar 

  • Hammer RE, Pursel VG, Rexroad CE et al (1985) Production of transgenic rabbits, sheep and pigs by microinjection. Nature 315:680–683

    Article  CAS  PubMed  Google Scholar 

  • Han H, Ma Y, Wang T et al (2014) One-step generation of myostatin gene knockout sheep via the CRISPR/Cas9 system. Front Agric Sci Eng 1:2–5

    Article  Google Scholar 

  • Hao F, Yan W, Li X et al (2018) Generation of cashmere goats carrying an EDAR gene mutant using CRISPR-Cas9-mediated genome editing. Int J Biol Sci 14:427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haruyama N, Cho A, Kulkarni AB (2009) Overview: engineering transgenic constructs and mice. Curr Protoc Cell Biol 42:19–10

    Article  Google Scholar 

  • He J, Li Q, Fang S et al (2015) PKD1 mono-allelic knockout is sufficient to trigger renal cystogenesis in a mini-pig model. Int J Biol Sci 11:361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He Z, Zhang T, Jiang L et al (2018) Use of CRISPR/Cas9 technology efficiently targetted goat myostatin through zygotes microinjection resulting in double-muscled phenotype in goats. Biosci Rep 38:BSR20180742

    Article  PubMed  PubMed Central  Google Scholar 

  • Hockemeyer D, Soldner F, Beard C et al (2009) Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases. Nat Biotechnol 27:851–857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hodges CA, Stice SL (2003) Generation of bovine transgenics using somatic cell nuclear transfer. Reprod Biol Endocrinol 1:1–7

    Article  Google Scholar 

  • Houdebine L-M (2005) Use of transgenic animals to improve human health and animal production. Reprod Domest Anim 40:269–281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Howarth JL, Lee YB, Uney JB (2010) Using viral vectors as gene transfer tools (Cell biology and toxicology special issue: ETCS-UK 1 day meeting on genetic manipulation of cells). Cell Biol Toxicol 26:1–20

    Article  CAS  PubMed  Google Scholar 

  • Hu S, Wang Z, Polejaeva I (2014) 40 knockout of goat nucleoporin 155 (NUP155) gene using CRISPR/Cas9 systems. Reprod Fertil Dev 26:134–134

    Article  Google Scholar 

  • Hu S, Yang M, Polejaeva I (2015) 360 double knockout of goat myostatin and prion protein gene using clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 systems. Reprod Fertil Dev 27:268–268

    Article  Google Scholar 

  • Hu R, Fan ZY, Wang BY et al (2017) RAPID COMMUNICATION: generation of FGF5 knockout sheep via the CRISPR/Cas9 system. J Anim Sci 95:2019–2024

    CAS  PubMed  Google Scholar 

  • Huang J, Guo X, Fan N et al (2014) RAG1/2 knockout pigs with severe combined immunodeficiency. J Immunol 193:1496–1503

    Article  CAS  PubMed  Google Scholar 

  • Huang L, Hua Z, Xiao H et al (2017) CRISPR/Cas9-mediated ApoE-/-and LDLR-/-double gene knockout in pigs elevates serum LDL-C and TC levels. Oncotarget 8:37751

    Article  PubMed  PubMed Central  Google Scholar 

  • Ikeda M, Matsuyama S, Akagi S et al (2017) Correction of a disease mutation using CRISPR/Cas9-assisted genome editing in Japanese black cattle. Sci Rep 7:1–9

    Article  Google Scholar 

  • Ivics Z, Izsvák Z (2010) The expanding universe of transposon technologies for gene and cell engineering. Mob DNA 1:1–15

    Article  Google Scholar 

  • Jakobsen JE, Li J, Moldt B et al (2011) Establishment of a pig fibroblast-derived cell line for locus-directed transgene expression in cell cultures and blastocysts. Mol Biol Rep 38:151–161

    Article  CAS  PubMed  Google Scholar 

  • Jakobsen JE, Johansen MG, Schmidt M et al (2013) Generation of minipigs with targeted transgene insertion by recombinase-mediated cassette exchange (RMCE) and somatic cell nuclear transfer (SCNT). Transgenic Res 22:709–723

    Article  CAS  PubMed  Google Scholar 

  • Jones JM, Meisler MH (2014) Modeling human epilepsy by TALEN targeting of mouse sodium channel Scn8a. Genesis 52:141–148

    Article  CAS  PubMed  Google Scholar 

  • Joung JK, Sander JD (2013) TALENs: a widely applicable technology for targeted genome editing. Nat Rev Mol Cell Biol 14:49–55

    Article  CAS  PubMed  Google Scholar 

  • Kalds P, Zhou S, Cai B et al (2019) Sheep and goat genome engineering: from random transgenesis to the CRISPR era. Front Genet 10:750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kang J-T, Ryu J, Cho B et al (2016) Generation of RUNX 3 knockout pigs using CRISPR/Cas9-mediated gene targeting. Reprod Domest Anim 51:970–978

    Article  CAS  PubMed  Google Scholar 

  • Kim Y-G, Chandrasegaran S (1994) Chimeric restriction endonuclease. Proc Natl Acad Sci 91:883–887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Laible G, Wei J, Wagner S (2015) Improving livestock for agriculture – technological progress from random transgenesis to precision genome editing heralds a new era. Biotechnol J 10:109–120. https://doi.org/10.1002/biot.201400193

    Article  CAS  PubMed  Google Scholar 

  • Lee K, Kwon D-N, Ezashi T et al (2014) Engraftment of human iPS cells and allogeneic porcine cells into pigs with inactivated RAG2 and accompanying severe combined immunodeficiency. Proc Natl Acad Sci 111:7260–7265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lei S, Ryu J, Wen K et al (2016) Increased and prolonged human norovirus infection in RAG2/IL2RG deficient gnotobiotic pigs with severe combined immunodeficiency. Sci Rep 6:1–12

    Article  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li F, Li Y, Liu H et al (2014a) Production of GHR double-allelic knockout Bama pig by TALENs and handmade cloning. Yi Chuan 36:903–911

    CAS  PubMed  Google Scholar 

  • Li F, Cowley DO, Banner D et al (2014b) Efficient genetic manipulation of the NOD-Rag1-/-IL2RgammaC-null mouse by combining in vitro fertilization and CRISPR/Cas9 technology. Sci Rep 4:1–7

    Google Scholar 

  • Li P, Estrada JL, Burlak C et al (2015) Efficient generation of genetically distinct pigs in a single pregnancy using multiplexed single-guide RNA and carbohydrate selection. Xenotransplantation 22:20–31

    Article  PubMed  Google Scholar 

  • Li W-R, Liu C-X, Zhang X-M et al (2017) CRISPR/Cas9-mediated loss of FGF5 function increases wool staple length in sheep. FEBS J 284:2764–2773

    Article  CAS  PubMed  Google Scholar 

  • Lillico SG, Sherman A, McGrew MJ et al (2007) Oviduct-specific expression of two therapeutic proteins in transgenic hens. Proc Natl Acad Sci 104:1771–1776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lillico SG, Proudfoot C, Carlson DF et al (2013) Live pigs produced from genome edited zygotes. Sci Rep 3:1–4

    Article  Google Scholar 

  • Liu C (2013) Strategies for designing transgenic DNA constructs. In: Lipoproteins and cardiovascular disease. Springer, pp 183–201

    Chapter  Google Scholar 

  • Liu C, Xie W, Gui C, Du Y (2013a) Pronuclear microinjection and oviduct transfer procedures for transgenic mouse production. In: Lipoproteins and cardiovascular disease. Springer, pp 217–232

    Chapter  Google Scholar 

  • Liu X, Wang Y, Guo W et al (2013b) Zinc-finger nickase-mediated insertion of the lysostaphin gene into the beta-casein locus in cloned cows. Nat Commun 4:1–11

    Article  Google Scholar 

  • Liu Y, Lv X, Tan R et al (2014a) A modified TALEN-based strategy for rapidly and efficiently generating knockout mice for kidney development studies. PLoS One 9:e84893

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu P, Long L, Xiong K et al (2014b) Heritable/conditional genome editing in C. elegans using a CRISPR-Cas9 feeding system. Cell Res 24:886–889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu X, Wang Y, Tian Y et al (2014c) Generation of mastitis resistance in cows by targeting human lysozyme gene to β-casein locus using zinc-finger nucleases. Proc R Soc B Biol Sci 281:20133368

    Article  Google Scholar 

  • Low BE, Krebs MP, Joung JK et al (2014) Correction of the Crb1rd8 allele and retinal phenotype in C57BL/6N mice via TALEN-mediated homology-directed repair. Invest Ophthalmol Vis Sci 55:387–395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luo J, Song Z, Yu S et al (2014) Efficient generation of myostatin (MSTN) biallelic mutations in cattle using zinc finger nucleases. PLoS One 9:e95225

    Article  PubMed  PubMed Central  Google Scholar 

  • Lutz AJ, Li P, Estrada JL et al (2013) Double knockout pigs deficient in N-glycolylneuraminic acid and G alactose α-1, 3-G alactose reduce the humoral barrier to xenotransplantation. Xenotransplantation 20:27–35

    Article  PubMed  Google Scholar 

  • Ma Y, Zhang X, Shen B et al (2014) Generating rats with conditional alleles using CRISPR/Cas9. Cell Res 24:122–125

    Article  CAS  PubMed  Google Scholar 

  • Maksimenko OG, Deykin AV, Georgiev PG (2013) Use of transgenic animals in biotechnology: prospects and problems. Acta Nat 5:33–46

    Article  CAS  Google Scholar 

  • Martello G, Smith A (2014) The nature of embryonic stem cells. Annu Rev Cell Dev Biol 30:647–675

    Article  CAS  PubMed  Google Scholar 

  • Menchaca A, Anegon I, Whitelaw CBA et al (2016) New insights and current tools for genetically engineered (GE) sheep and goats. Theriogenology 86:160–169

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meyer M, Ortiz O, de Angelis MH et al (2012) Modeling disease mutations by gene targeting in one-cell mouse embryos. Proc Natl Acad Sci 109:9354–9359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Mochizuki Y, Chiba T, Kataoka K et al (2018) Combinatorial CRISPR/Cas9 approach to elucidate a far-upstream enhancer complex for tissue-specific Sox9 expression. Dev Cell 46:794–806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mohammed F, Shibbiru T, Mengistu A, Tadesse F (2016) Transgenic animal technology: technique and its application to improve animal productivity. Adv Life Sci Technol 48:35

    Google Scholar 

  • Mojica FJ, Díez-Villaseñor C, Soria E, Juez G (2000) Biological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria. Mol Microbiol 36:244–246

    Article  CAS  PubMed  Google Scholar 

  • Mojica FJ, García-Martínez J, Soria E (2005) Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. J Mol Evol 60:174–182

    Article  CAS  PubMed  Google Scholar 

  • Moltó E, Vicente-García C, Fernández A, Montoliu L (2011) Genomic insulators in transgenic animals. In: Mouse as a model organism. Springer, pp 1–10

    Google Scholar 

  • Naeem M, Majeed S, Hoque MZ, Ahmad I (2020) Latest developed strategies to minimize the off-target effects in CRISPR-Cas-mediated genome editing. Cells 9:1608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nanjidsuren T, Park C-W, Sim B-W et al (2016) GRK5-knockout mice generated by TALEN-mediated gene targeting. Anim Biotechnol 27:223–230

    Article  CAS  PubMed  Google Scholar 

  • Ni W, Qiao J, Hu S et al (2014) Efficient gene knockout in goats using CRISPR/Cas9 system. PLoS One 9:e106718

    Article  PubMed  PubMed Central  Google Scholar 

  • Niu Y, Shen B, Cui Y et al (2014) Generation of gene-modified cynomolgus monkey via Cas9/RNA-mediated gene targeting in one-cell embryos. Cell 156:836–843

    Article  CAS  PubMed  Google Scholar 

  • Niu Y, Jin M, Li Y et al (2017) Biallelic β-carotene oxygenase 2 knockout results in yellow fat in sheep via CRISPR/Cas9. Anim Genet 48:242–244

    Article  CAS  PubMed  Google Scholar 

  • Ostedgaard LS, Price MP, Whitworth KM et al (2020) Lack of airway submucosal glands impairs respiratory host defenses. elife 9:e59653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Panda SK, Wefers B, Ortiz O et al (2013) Highly efficient targeted mutagenesis in mice using TALENs. Genetics 195:703–713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pattanayak V, Lin S, Guilinger JP et al (2013) High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity. Nat Biotechnol 31:839–843

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 26:808–816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perisse IV, Fan Z, Singina GN et al (2020) Improvements in gene editing technology boost its applications in livestock. Front Genet 11:614688

    Article  CAS  PubMed  Google Scholar 

  • Perota A, Lagutina I, Duchi R et al (2019) Generation of cattle knockout for galactose-α1, 3-galactose and N-glycolylneuraminic acid antigens. Xenotransplantation 26:e12524

    Article  PubMed  PubMed Central  Google Scholar 

  • Pfeifer A (2004) Lentiviral transgenesis. Transgenic Res 13:513–522

    Article  CAS  PubMed  Google Scholar 

  • Pfeifer A (2006) Lentiviral transgenesis-a versatile tool for basic research and gene therapy. Curr Gene Ther 6:535–542

    Article  CAS  PubMed  Google Scholar 

  • Pfeifer A, Hofmann A (2009) Lentiviral transgenesis. In: Gene knockout protocols. Springer, pp 391–405

    Chapter  Google Scholar 

  • Pfeifer A, Ikawa M, Dayn Y, Verma IM (2002) Transgenesis by lentiviral vectors: lack of gene silencing in mammalian embryonic stem cells and preimplantation embryos. Proc Natl Acad Sci 99:2140–2145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Platt RJ, Chen S, Zhou Y et al (2014) CRISPR-Cas9 knockin mice for genome editing and cancer modeling. Cell 159:440–455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Proudfoot C, Carlson DF, Huddart R et al (2015) Genome edited sheep and cattle. Transgenic Res 24:147–153

    Article  CAS  PubMed  Google Scholar 

  • Qian L, Tang M, Yang J et al (2015) Targeted mutations in myostatin by zinc-finger nucleases result in double-muscled phenotype in Meishan pigs. Sci Rep 5:1–13

    Article  Google Scholar 

  • Rao S, Fujimura T, Matsunari H et al (2016) Efficient modification of the myostatin gene in porcine somatic cells and generation of knockout piglets. Mol Reprod Dev 83:61–70

    Article  CAS  PubMed  Google Scholar 

  • Rashid T, Kobayashi T, Nakauchi H (2014) Revisiting the flight of Icarus: making human organs from PSCs with large animal chimeras. Cell Stem Cell 15:406–409

    Article  CAS  PubMed  Google Scholar 

  • Rauch F, Geng Y, Lamplugh L et al (2018) Crispr-Cas9 engineered osteogenesis imperfecta type V leads to severe skeletal deformities and perinatal lethality in mice. Bone 107:131–142

    Article  CAS  PubMed  Google Scholar 

  • Recillas-Targa F (2006) Multiple strategies for gene transfer, expression, knockdown, and chromatin influence in mammalian cell lines and transgenic animals. Mol Biotechnol 34:337–354

    Article  CAS  PubMed  Google Scholar 

  • Remy S, Nguyen TH, Ménoret S et al (2010) The use of lentiviral vectors to obtain transgenic rats. In: Rat genomics. Springer, pp 109–125

    Chapter  Google Scholar 

  • Ritchie WA, King T, Neil C et al (2009) Transgenic sheep designed for transplantation studies. Mol Reprod Dev 76:61–64

    Article  CAS  PubMed  Google Scholar 

  • Rocha-Martins M, Cavalheiro GR, Matos-Rodrigues GE, Martins RA (2015) From gene targeting to genome editing: transgenic animals applications and beyond. An Acad Bras Cienc 87:1323–1348

    Article  CAS  PubMed  Google Scholar 

  • Ruan J, Xu J, Chen-Tsai RY, Li K (2017) Genome editing in livestock: are we ready for a revolution in animal breeding industry? Transgenic Res 26:715–726

    Article  CAS  PubMed  Google Scholar 

  • Ryding AD, Sharp MG, Mullins JJ (2001) Conditional transgenic technologies. J Endocrinol 171:1–14

    Article  CAS  PubMed  Google Scholar 

  • Schnieke AE, Kind AJ, Ritchie WA et al (1997) Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts. Science 278:2130–2133

    Article  CAS  PubMed  Google Scholar 

  • Schuster F, Aldag P, Frenzel A et al (2020) CRISPR/Cas12a mediated knock-in of the Polled Celtic variant to produce a polled genotype in dairy cattle. Sci Rep 10:1–9

    Article  Google Scholar 

  • Shepelev MV, Kalinichenko SV, Deykin AV, Korobko IV (2018) Production of recombinant proteins in the milk of transgenic animals: current state and prospects. Acta Nat 10:40–47

    Article  CAS  Google Scholar 

  • Sommer D, Peters AE, Wirtz T et al (2014) Efficient genome engineering by targeted homologous recombination in mouse embryos using transcription activator-like effector nucleases. Nat Commun 5:1–12

    Article  Google Scholar 

  • Song C-Q, Jiang T, Richter M et al (2020) Adenine base editing in an adult mouse model of tyrosinaemia. Nat Biomed Eng 4:125–130

    Article  CAS  PubMed  Google Scholar 

  • Sun N, Zhao H (2013) Transcription activator-like effector nucleases (TALENs): a highly efficient and versatile tool for genome editing. Biotechnol Bioeng 110:1811–1821

    Article  CAS  PubMed  Google Scholar 

  • Sun Z, Wang M, Han S et al (2018) Production of hypoallergenic milk from DNA-free beta-lactoglobulin (BLG) gene knockout cow using zinc-finger nucleases mRNA. Sci Rep 8:1–11

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Tan W, Carlson DF, Lancto CA et al (2013) Efficient nonmeiotic allele introgression in livestock using custom endonucleases. Proc Natl Acad Sci 110:16526–16531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tan W, Proudfoot C, Lillico SG, Whitelaw CBA (2016) Gene targeting, genome editing: from Dolly to editors. Transgenic Res 25:273–287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tanihara F, Hirata M, Nguyen NT et al (2020) Efficient generation of GGTA1-deficient pigs by electroporation of the CRISPR/Cas9 system into in vitro-fertilized zygotes. BMC Biotechnol 20:1–11

    Article  Google Scholar 

  • Tanihara F, Hirata M, Nguyen NT et al (2021) Generation of CD163-edited pig via electroporation of the CRISPR/Cas9 system into porcine in vitro-fertilized zygotes. Anim Biotechnol 32:147–154

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Vilarino M, Rashid ST, Suchy FP et al (2017) CRISPR/Cas9 microinjection in oocytes disables pancreas development in sheep. Sci Rep 7:1–10

    Article  CAS  Google Scholar 

  • Wang H, Yang H, Shivalila CS et al (2013) One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell 153:910–918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang S, Sengel C, Emerson MM, Cepko CL (2014) A gene regulatory network controls the binary fate decision of rod and bipolar cells in the vertebrate retina. Dev Cell 30:513–527

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang X, Yu H, Lei A et al (2015) Generation of gene-modified goats targeting MSTN and FGF5 via zygote injection of CRISPR/Cas9 system. Sci Rep 5:1–9

    Google Scholar 

  • Wang X, Niu Y, Zhou J et al (2016a) Multiplex gene editing via CRISPR/Cas9 exhibits desirable muscle hypertrophy without detectable off-target effects in sheep. Sci Rep 6:1–11

    Google Scholar 

  • Wang X, Cao C, Huang J et al (2016b) One-step generation of triple gene-targeted pigs using CRISPR/Cas9 system. Sci Rep 6:1–7

    Google Scholar 

  • Wang K, Tang X, Xie Z et al (2017) CRISPR/Cas9-mediated knockout of myostatin in Chinese indigenous Erhualian pigs. Transgenic Res 26:799–805

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Liu M, Zhao L et al (2019) Disabling of nephrogenesis in porcine embryos via CRISPR/Cas9-mediated SIX1 and SIX4 gene targeting. Xenotransplantation 26:e12484

    Article  PubMed  Google Scholar 

  • Watanabe M, Nakano K, Matsunari H et al (2013) Generation of interleukin-2 receptor gamma gene knockout pigs from somatic cells genetically modified by zinc finger nuclease-encoding mRNA. PLoS One 8:e76478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wefers B, Meyer M, Ortiz O et al (2013) Direct production of mouse disease models by embryo microinjection of TALENs and oligodeoxynucleotides. Proc Natl Acad Sci 110:3782–3787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wells DN (2005) Animal cloning: problems and prospects. Rev Sci Tech 24:251

    Article  CAS  PubMed  Google Scholar 

  • Whitworth KM, Lee K, Benne JA et al (2014) Use of the CRISPR/Cas9 system to produce genetically engineered pigs from in vitro-derived oocytes and embryos. Biol Reprod 91:78–71

    Article  PubMed  PubMed Central  Google Scholar 

  • Whitworth KM, Rowland RR, Ewen CL et al (2016) Gene-edited pigs are protected from porcine reproductive and respiratory syndrome virus. Nat Biotechnol 34:20–22

    Article  CAS  PubMed  Google Scholar 

  • Williams DK, Pinzón C, Huggins S et al (2018) Genetic engineering a large animal model of human hypophosphatasia in sheep. Sci Rep 8:1–10

    Article  Google Scholar 

  • Wu H, Wang Y, Zhang Y et al (2015) TALE nickase-mediated SP110 knockin endows cattle with increased resistance to tuberculosis. Proc Natl Acad Sci 112:E1530–E1539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu M, Wei C, Lian Z et al (2016) Rosa26-targeted sheep gene knock-in via CRISPR-Cas9 system. Sci Rep 6:1–7

    Google Scholar 

  • Wu J, Vilarino M, Suzuki K et al (2017) CRISPR-Cas9 mediated one-step disabling of pancreatogenesis in pigs. Sci Rep 7:1–6

    Google Scholar 

  • Xiang G, Ren J, Hai T et al (2018) Editing porcine IGF2 regulatory element improved meat production in Chinese Bama pigs. Cell Mol Life Sci 75:4619–4628

    Article  CAS  PubMed  Google Scholar 

  • Xin J, Yang H, Fan N et al (2013) Highly efficient generation of GGTA1 biallelic knockout inbred mini-pigs with TALENs. PLoS One 8:e84250

    Article  PubMed  PubMed Central  Google Scholar 

  • Yan S, Tu Z, Liu Z et al (2018) A huntingtin knockin pig model recapitulates features of selective neurodegeneration in Huntington’s disease. Cell 173:989–1002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang H, Wu Z (2018) Genome editing of pigs for agriculture and biomedicine. Front Genet 9:360

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang D, Yang H, Li W et al (2011) Generation of PPARγ mono-allelic knockout pigs via zinc-finger nucleases and nuclear transfer cloning. Cell Res 21:979–998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang H, Wang H, Shivalila CS et al (2013) One-step generation of mice carrying reporter and conditional alleles by CRISPR/Cas-mediated genome engineering. Cell 154:1370–1379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang H, Zhang J, Zhang X et al (2018) CD163 knockout pigs are fully resistant to highly pathogenic porcine reproductive and respiratory syndrome virus. Antivir Res 151:63–70

    Article  CAS  PubMed  Google Scholar 

  • Yao J, Huang J, Hai T et al (2014) Efficient bi-allelic gene knockout and site-specific knock-in mediated by TALENs in pigs. Sci Rep 4:1–8

    Article  Google Scholar 

  • Yi D, Zhou S, Qiang D et al (2020) The CRISPR/Cas9 induces large genomic fragment deletions of MSTN and phenotypic changes in sheep. J Integr Agric 19:1065–1073

    Article  Google Scholar 

  • Yu S, Luo J, Song Z et al (2011) Highly efficient modification of beta-lactoglobulin (BLG) gene via zinc-finger nucleases in cattle. Cell Res 21:1638–1640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang S, Li L, Kendrick SL et al (2014) TALEN-mediated somatic mutagenesis in murine models of cancer. Cancer Res 74:5311–5321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang X, Li W, Liu C et al (2017) Alteration of sheep coat color pattern by disruption of ASIP gene via CRISPR Cas9. Sci Rep 7:1–10

    Google Scholar 

  • Zhang R, Wang Y, Chen L et al (2018) Reducing immunoreactivity of porcine bioprosthetic heart valves by genetically-deleting three major glycan antigens, GGTA1/β4GalNT2/CMAH. Acta Biomater 72:196–205

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Wang Y, Yulin B et al (2019) CRISPR/Cas9-mediated sheep MSTN gene knockout and promote sSMSCs differentiation. J Cell Biochem 120:1794–1806

    Article  CAS  PubMed  Google Scholar 

  • Zhang R, Li Y, Jia K et al (2020) Crosstalk between androgen and Wnt/β-catenin leads to changes of wool density in FGF5-knockout sheep. Cell Death Dis 11:1–12

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhou X, Xin J, Fan N et al (2015) Generation of CRISPR/Cas9-mediated gene-targeted pigs via somatic cell nuclear transfer. Cell Mol Life Sci 72:1175–1184

    Article  CAS  PubMed  Google Scholar 

  • Zhou W, Wan Y, Guo R et al (2017) Generation of beta-lactoglobulin knock-out goats using CRISPR/Cas9. PLoS One 12:e0186056

    Article  PubMed  PubMed Central  Google Scholar 

  • Zou Y, Li Z, Zou Y et al (2018) An FBXO40 knockout generated by CRISPR/Cas9 causes muscle hypertrophy in pigs without detectable pathological effects. Biochem Biophys Res Commun 498:940–945

    Article  CAS  PubMed  Google Scholar 

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Saugandhika, S., Jain, N. (2024). Evolution of Transgenic Technology: From Random Transgenesis to Precise Genome Editing. In: Kumar Yata, V., Mohanty, A.K., Lichtfouse, E. (eds) Sustainable Agriculture Reviews . Sustainable Agriculture Reviews, vol 62. Springer, Cham. https://doi.org/10.1007/978-3-031-54372-2_3

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