Abstract
Gene editing techniques were developed chronologically, which include zinc finger nuclease, transcription activator-like effector nuclease and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas 9). In this review, the working principles of these techniques were first introduced, their advantages and disadvantages were then discussed, their application in animal husbandry were elaborated, and finally human concerns about gene editing were presented. Compared to the two former techniques, the third-generation gene editing technique CRISPR/Cas9 has higher targeting efficiency and accuracy, less off-target effect, lower cytotoxicity and lower costs for being easier for vector design and manipulation. Although some people may concern about social or ethical issues, the benefits of gene editing certainly overweigh its demerits. The three gene editing techniques have been successfully used to improve the production and quality of livestock products, animal fertility, resistance to diseases, and welfare in animal husbandry. With legislation and the development of gene editing technology per se, it anticipatable that gene editing will have a broader utilization and make our lives happier.
Similar content being viewed by others
References
Boch J, Bonas U (2010) Xanthomonas AvrBs3 family-type III effectors: discovery and function. Ann Rev Phytopathol 48:419–436. https://doi.org/10.1146/annurev-phyto-080508-081936
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. https://doi.org/10.1126/science.1178811
Bolotin A, Quinquis B, Sorokin A, Ehrlich SD (2005) Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. Microbiology 151(Pt 8):2551–2561. https://doi.org/10.1099/mic.0.28048-0
Bonas U, Stall RE, Staskawicz B (1989) Genetic and structural characterization of the avirulence gene avrBs3 from Xanthomonas campestris pv. vesicatoria. Mol Gen Genetics MGG 218(1):127–136
Burkard C, Lillico SG, Reid E, Jackson B, Mileham AJ, Ait-Ali T, Whitelaw CB, Archibald AL (2017) Precision engineering for PRRSV resistance in pigs: macrophages from genome edited pigs lacking CD163 SRCR5 domain are fully resistant to both PRRSV genotypes while maintaining biological function. PLoS Pathogens 13(2):e1006206. https://doi.org/10.1371/journal.ppat.1006206
Carlson DF, Lancto CA, Zang B, Kim ES, Walton M, Oldeschulte D, Seabury C, Sonstegard TS, Fahrenkrug SC (2016) Production of hornless dairy cattle from genome-edited cell lines. Nat Biotechnol 34(5):479–481. https://doi.org/10.1038/nbt.3560
Chen JS, Dagdas YS, Kleinstiver BP, Welch MM, Sousa AA, Harrington LB, Sternberg SH, Joung JK, Yildiz A, Doudna JA (2017) Enhanced proofreading governs CRISPR-Cas9 targeting accuracy. Nature 550(7676):407–410. https://doi.org/10.1038/nature24268
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. https://doi.org/10.1126/science.1231143
Crispo M, Mulet AP, Tesson L, Barrera N, Cuadro F, dos Santos-Neto PC, Nguyen TH, Creneguy A, Brusselle L, Anegon I, Menchaca A (2015) Efficient generation of myostatin knock-out sheep using CRISPR/Cas9 technology and microinjection into zygotes. PloS One 10(8):e0136690. https://doi.org/10.1371/journal.pone.0136690
Davis D, Stokoe D (2010) Zinc finger nucleases as tools to understand and treat human diseases. BMC Med 8:42. https://doi.org/10.1186/1741-7015-8-42
Ding Q, Regan SN, Xia Y, Oostrom LA, Cowan CA, Musunuru K (2013) Enhanced efficiency of human pluripotent stem cell genome editing through replacing TALENs with CRISPRs. Cell Stem Cell 12(4):393–394. https://doi.org/10.1016/j.stem.2013.03.006
Fu Y, Foden JA, Khayter C, Maeder ML, Reyon D, Joung JK, Sander JD (2013) High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nat Biotechnol 31(9):822–826. https://doi.org/10.1038/nbt.2623
Fujii W, Kano K, Sugiura K, Naito K (2013) Repeatable construction method for engineered zinc finger nuclease based on overlap extension PCR and TA-cloning. PloS One 8(3):e59801. https://doi.org/10.1371/journal.pone.0059801
Fujii W, Onuma A, Yoshioka S, Nagashima K, Sugiura K, Naito K (2015) Finding of a highly efficient ZFN pair for Aqpep gene functioning in murine zygotes. J Reprod Dev 61(6):589–593. https://doi.org/10.1262/jrd.2015-087
Gaind N (2016) Brain implants and gene-editing enhancements worry US public. Nature. https://doi.org/10.1038/nature.2016.20350
Gandhi PT, Athmaram TN, Arunkumar GR (2016) Novel nicotine analogues with potential anti-mycobacterial activity. Bioorg Med Chem 24(8):1637–1647. https://doi.org/10.1016/j.bmc.2016.02.035
Heyer WD, Ehmsen KT, Liu J (2010) Regulation of homologous recombination in eukaryotes. Ann Rev Genetics 44:113–139. https://doi.org/10.1146/annurev-genet-051710-150955
Ishino Y, Shinagawa H, Makino K, Amemura M, Nakata A (1987) Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. J Bacteriol 169(12):5429–5433
Jarman AP, Grau Y, Jan LY, Jan YN (1993) atonal is a proneural gene that directs chordotonal organ formation in the Drosophila peripheral nervous system. Cell 73(7):1307–1321
Jin L, Deng Y, He N, Wang L, Weng M (2018) Polyethylenimine-mediated CCR5 gene knockout using transcription activator-like effector nucleases. J Biomed Nanotechnol 14(3):546–552. https://doi.org/10.1166/jbn.2018.2545
Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E (2012) A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337(6096):816–821. https://doi.org/10.1126/science.1225829
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
Klug A (2010) The discovery of zinc fingers and their development for practical applications in gene regulation and genome manipulation. Quart Rev Biophys 43(1):1–21. https://doi.org/10.1017/s0033583510000089
Ledford H (2017) Gene-edited cows, rogue clinics, speedier drug approvals: the challenges facing Trump’s FDA chief. Nature 541(7636):146–147. https://doi.org/10.1038/nature.2017.21256
Lei Y, Guo X, Liu Y, Cao Y, Deng Y, Chen X, Cheng CH, Dawid IB, Chen Y, Zhao H (2012) Efficient targeted gene disruption in Xenopus embryos using engineered transcription activator-like effector nucleases (TALENs). Proc Natl Acad Sci USA 109(43):17484–17489. https://doi.org/10.1073/pnas.1215421109
Li T, Liu B, Spalding MH, Weeks DP, Yang B (2012) High-efficiency TALEN-based gene editing produces disease-resistant rice. Nat Biotechnol 30(5):390–392. https://doi.org/10.1038/nbt.2199
Li H, Wang G, Hao Z, Zhang G, Qing Y, Liu S, Qing L, Pan W, Chen L, Liu G, Zhao R, Jia B, Zeng L, Guo J, Zhao L, Zhao H, Lv C, Xu K, Cheng W, Li H, Zhao HY, Wang W, Wei HJ (2016) Generation of biallelic knock-out sheep via gene-editing and somatic cell nuclear transfer. Sci Rep 6:33675. https://doi.org/10.1038/srep33675
Li M, Ouyang H, Yuan H, Li J, Xie Z, Wang K, Yu T, Liu M, Chen X, Tang X, Jiao H, Pang D. (Bethesda (2018) Site-specific Fat-1 knock-in enables significant decrease of n-6PUFAs/n-3PUFAs ratio in pigs. G3 (Bethesda, Md) 8(5):1747–1754. https://doi.org/10.1534/g3.118.200114
Liu J, Gaj T, Wallen MC, Barbas CF 3rd (2015) Improved cell-penetrating zinc-finger nuclease proteins for precision genome engineering. Mol Ther Nucleic Acids 4:e232. https://doi.org/10.1038/mtna.2015.6
Luo J, Song Z, Yu S, Cui D, Wang B, Ding F, Li S, Dai Y, Li N (2014) Efficient generation of myostatin (MSTN) biallelic mutations in cattle using zinc finger nucleases. PloS One 9(4):e95225. https://doi.org/10.1371/journal.pone.0095225
Ma S, Chang J, Wang X, Liu Y, Zhang J, Lu W, Gao J, Shi R, Zhao P, Xia Q (2014) CRISPR/Cas9 mediated multiplex genome editing and heritable mutagenesis of BmKu70 in Bombyx mori. Sci Rep 4:4489. https://doi.org/10.1038/srep04489
Makarova KS, Grishin NV, Shabalina SA, Wolf YI, Koonin EV (2006) A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action. Biol Direct 1:7. https://doi.org/10.1186/1745-6150-1-7
Mao C, Tao Y (2015) Current progress of genome editing techniques. Chem Life 35(1):96–104. https://doi.org/10.13488/j.smhx.20150117
Mojica FJ, Diez-Villasenor C, Garcia-Martinez J, Soria E (2005) Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. J Mol Evol 60(2):174–182. https://doi.org/10.1007/s00239-004-0046-3
Moscou MJ, Bogdanove AJ (2009) A simple cipher governs DNA recognition by TAL effectors. Science 326(5959):1501. https://doi.org/10.1126/science.1178817
Nerys-Junior A, Braga-Dias LP, Pezzuto P, Cotta-de-Almeida V, Tanuri A (2018) Comparison of the editing patterns and editing efficiencies of TALEN and CRISPR-Cas9 when targeting the human CCR5 gene. Genetics Mol Biol 41(1):167–179. https://doi.org/10.1590/1678-4685-gmb-2017-0065
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
Pourcel C, Salvignol G, Vergnaud G (2005) CRISPR elements in Yersinia pestis acquire new repeats by preferential uptake of bacteriophage DNA, and provide additional tools for evolutionary studies. Microbiology 151(Pt 3):653–663. https://doi.org/10.1099/mic.0.27437-0
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. https://doi.org/10.1007/s11248-014-9832-x
Qian L, Tang M, Yang J, Wang Q, Cai C, Jiang S, Li H, Jiang K, Gao P, Ma D, Chen Y, An X, Li K, Cui W (2015) Targeted mutations in myostatin by zinc-finger nucleases result in double-muscled phenotype in Meishan pigs. Sci Rep 5:14435. https://doi.org/10.1038/srep14435
Qiu Z, Liu M, Chen Z, Shao Y, Pan H, Wei G, Yu C, Zhang L, Li X, Wang P, Fan HY, Du B, Liu B, Liu M, Li D (2013) High-efficiency and heritable gene targeting in mouse by transcription activator-like effector nucleases. Nucleic Acids Res 41(11):e120. https://doi.org/10.1093/nar/gkt258
Ricroch AE, Henard-Damave MC (2016) Next biotech plants: new traits, crops, developers and technologies for addressing global challenges. Crit Rev Biotechnol 36(4):675–690. https://doi.org/10.3109/07388551.2015.1004521
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(6):715–726. https://doi.org/10.1007/s11248-017-0049-7
Sander JD, Dahlborg EJ, Goodwin MJ, Cade L, Zhang F, Cifuentes D, Curtin SJ, Blackburn JS, Thibodeau-Beganny S, Qi Y, Pierick CJ, Hoffman E, Maeder ML, Khayter C, Reyon D, Dobbs D, Langenau DM, Stupar RM, Giraldez AJ, Voytas DF, Peterson RT, Yeh JR, Joung JK (2011) Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA). Nat Methods 8(1):67–69. https://doi.org/10.1038/nmeth.1542
Shukla VK, Doyon Y, Miller JC, DeKelver RC, Moehle EA, Worden SE, Mitchell JC, Arnold NL, Gopalan S, Meng X, Choi VM, Rock JM, Wu YY, Katibah GE, Zhifang G, McCaskill D, Simpson MA, Blakeslee B, Greenwalt SA, Butler HJ, Hinkley SJ, Zhang L, Rebar EJ, Gregory PD, Urnov FD (2009) Precise genome modification in the crop species Zea mays using zinc-finger nucleases. Nature 459(7245):437–441. https://doi.org/10.1038/nature07992
Soldner F, Laganiere J, Cheng AW, Hockemeyer D, Gao Q, Alagappan R, Khurana V, Golbe LI, Myers RH, Lindquist S, Zhang L, Guschin D, Fong LK, Vu BJ, Meng X, Urnov FD, Rebar EJ, Gregory PD, Zhang HS, Jaenisch R (2011) Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations. Cell 146(2):318–331. https://doi.org/10.1016/j.cell.2011.06.019
Stern A, Keren L, Wurtzel O, Amitai G, Sorek R (2010) Self-targeting by CRISPR: gene regulation or autoimmunity? Trends Genetics TIG 26 (8):335–340. https://doi.org/10.1016/j.tig.2010.05.008
Sugano SS, Nishihama R, Shirakawa M, Takagi J, Matsuda Y, Ishida S, Shimada T, Hara-Nishimura I, Osakabe K, Kohchi T (2018) Efficient CRISPR/Cas9-based genome editing and its application to conditional genetic analysis in Marchantia polymorpha. bioRxiv 13(10):e0205117. https://doi.org/10.1371/journal.pone.0205117
Sung YH, Jin Y, Kim S, Lee HW (2014) Generation of knockout mice using engineered nucleases. Methods 69(1):85–93. https://doi.org/10.1016/j.ymeth.2014.02.009
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. https://doi.org/10.1038/nbt.1940
Townsend JA, Wright DA, Winfrey RJ, Fu F, Maeder ML, Joung JK, Voytas DF (2009) High-frequency modification of plant genes using engineered zinc-finger nucleases. Nature 459(7245):442–445. https://doi.org/10.1038/nature07845
Wang X, Cai B, Zhou J, Zhu H, Niu Y, Ma B, Yu H, Lei A, Yan H, Shen Q, Shi L, Zhao X, Hua J, Huang X, Qu L, Chen Y (2016a) Correction: disruption of FGF5 in cashmere goats using CRISPR/Cas9 results in more secondary hair follicles and longer fibers. PloS One 11(11):e0167322. https://doi.org/10.1371/journal.pone.0167322
Wang X, Niu Y, Zhou J, Yu H, Kou Q, Lei A, Zhao X, Yan H, Cai B, Shen Q, Zhou S, Zhu H, Zhou G, Niu W, Hua J, Jiang Y, Huang X, Ma B, Chen Y (2016b) Multiplex gene editing via CRISPR/Cas9 exhibits desirable muscle hypertrophy without detectable off-target effects in sheep. Sci Rep 6:32271. https://doi.org/10.1038/srep32271
Wei Y, Chesne MT, Terns RM, Terns MP (2015) Sequences spanning the leader-repeat junction mediate CRISPR adaptation to phage in Streptococcus thermophilus. Nucleic Acids Res 43(3):1749–1758. https://doi.org/10.1093/nar/gku1407
Wright DA, Li T, Yang B, Spalding MH (2014) TALEN-mediated genome editing: prospects and perspectives. Biochem J 462(1):15–24. https://doi.org/10.1042/bj20140295
Wu H, Wang Y, Zhang Y, Yang M, Lv J, Liu J, Zhang Y (2015) TALE nickase-mediated SP110 knockin endows cattle with increased resistance to tuberculosis. Proc Natl Acad Sci USA 112(13):E1530–E1539. https://doi.org/10.1073/pnas.1421587112
Xiao A, Hu YY, Wang WY, Yang ZP, Wang ZX, Huang P, Tong XJ, Zhang B, Lin S (2011) Progress in zinc finger nuclease engineering for targeted genome modification. Yi chuan = Hereditas 33(7):665–683
Xu L, Yang H, Gao Y, Chen Z, Xie L, Liu Y, Liu Y, Wang X, Li H, Lai W, He Y, Yao A, Ma L, Shao Y, Zhang B, Wang C, Chen H, Deng H (2017) CRISPR/Cas9-mediated CCR5 ablation in human hematopoietic stem/progenitor cells confers HIV-1 resistance in vivo. Mol Ther 25(8):1782–1789. https://doi.org/10.1016/j.ymthe.2017.04.027
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. https://doi.org/10.1038/cr.2011.153
Yu B, Lu R, Yuan Y, Zhang T, Song S, Qi Z, Shao B, Zhu M, Mi F, Cheng Y (2016) Efficient TALEN-mediated myostatin gene editing in goats. BMC Dev Biol 16(1):26. https://doi.org/10.1186/s12861-016-0126-9
Zhang K, Raboanatahiry N, Zhu B, Li M (2017) Progress in genome editing technology and its application in plants. Front Plant Sci 8:177. https://doi.org/10.3389/fpls.2017.00177
Zhang J, Cui ML, Nie YW, Dai B, Li FR, Liu DJ, Liang H, Cang M (2018) CRISPR/Cas9-mediated specific integration of fat-1 at the goat MSTN locus. FEBS J 285(15):2828–2839. https://doi.org/10.1111/febs.14520
Zhou W, Wan Y, Guo R, Deng M, Deng K, Wang Z, Zhang Y, Wang F (2017) Generation of beta-lactoglobulin knock-out goats using CRISPR/Cas9. PloS One 12(10):e0186056. https://doi.org/10.1371/journal.pone.0186056
Acknowledgements
This work was supported by National Natural Science Foundation of China (Grant number 31571862).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
Rights and permissions
About this article
Cite this article
Jiang, S., Shen, Q.W. Principles of gene editing techniques and applications in animal husbandry. 3 Biotech 9, 28 (2019). https://doi.org/10.1007/s13205-018-1563-x
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s13205-018-1563-x