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References
Adiguzel C, Iqbal O, Demir M, Fareed J (2009) European community and US-FDA approval of recombinant human antithrombin produced in genetically altered goats. Clin Appl Thromb Hemost 15(6):645–651. https://doi.org/10.1177/1076029609339748
Angel MA, Gil MA, Cuello C, Sanchez-Osorio J, Gomis J, Parrilla I, Vila J, Colina I, Diaz M, Reixach J, Vazquez JL, Vazquez JM, Roca J, Martinez EA (2014) An earlier uterine environment favors the in vivo development of fresh pig morulae and blastocysts transferred by a nonsurgical deep-uterine method. J Reprod Dev 60(5):371–376
Bai J, Lin H, Li H, Zhou Y, Liu J, Zhong G, Wu L, Jiang W, Du H, Yang J, Xie Q, Huang L (2019) Cas12a-Based On-Site and Rapid Nucleic Acid Detection of African Swine Fever. Front Microbiol 10:2830. https://doi.org/10.3389/fmicb.2019.02830
Beaujean N, Jammes H, Jouneau A (2015) Nuclear reprogramming: methods and protocols. methods in molecular biology, Methods and protocols,1222, 2nd edn. Springer New York, New York
Bertolini LR, Meade H, Lazzarotto CR, Martins LT, Tavares KC, Bertolini M, Murray JD (2016) The transgenic animal platform for biopharmaceutical production. Transgenic Res 25(3):329–343. https://doi.org/10.1007/s11248-016-9933-9
Bibikova M, Carroll D, Segal DJ, Trautman JK, Smith J, Kim YG, Chandrasegaran S (2001) Stimulation of homologous recombination through targeted cleavage by chimeric nucleases. Mol Cell Biol 21(1):289–297. https://doi.org/10.1128/MCB.21.1.289-297.2001
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
Bloom K, Ely A, Arbuthnot P (2017) A T7 endonuclease I assay to detect talen-mediated targeted mutation of HBV cccDNA. In: Methods in molecular biology, vol 1540. Humana Press Inc., pp 85–95. https://doi.org/10.1007/978-1-4939-6700-1_8
Boas FE, Nurili F, Bendet A, Cheleuitte-Nieves C, Basturk O, Askan G, Michel AO, Monette S, Ziv E, Sofocleous CT, Maxwell AWP, Schook LB, Solomon SB, Kelsen DP, Scherz A, Yarmohammadi H (2020) Induction and characterization of pancreatic cancer in a transgenic pig model. PLoS One 15(9):e0239391. https://doi.org/10.1371/journal.pone.0239391
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
Boettcher AN, Li Y, Ahrens AP, Kiupel M, Byrne KA, Loving CL, Cino-Ozuna AG, Wiarda JE, Adur M, Schultz B, Swanson JJ, Snella EM, Ho CS, Charley SE, Kiefer ZE, Cunnick JE, Putz EJ, Dell'Anna G, Jens J, Sathe S, Goldman F, Westin ER, Dekkers JCM, Ross JW, Tuggle CK (2020) Novel Engraftment and T Cell Differentiation of Human Hematopoietic Cells in ART (-/-) IL2RG (-/Y) SCID Pigs. Front Immunol 11:100. https://doi.org/10.3389/fimmu.2020.00100
Borca MV, Holinka LG, Berggren KA, Gladue DP (2018) CRISPR-Cas9, a tool to efficiently increase the development of recombinant African swine fever viruses. Scientific Rep 8(1):3154. https://doi.org/10.1038/s41598-018-21575-8
Brem G, Brenig B, Goodman HM, Selden RC, Graf F, Kruff B, Springman K, Hondele J, Meyer J, Winnacker EL, Kräußlich H (1985) Production of transgenic mice, rabbits and pigs by microinjection into pronuclei. Reprod Domest Anim 20(4):251–252. https://doi.org/10.1111/j.1439-0531.1985.tb00423.x
Brinkman EK, Kousholt AN, Harmsen T, Leemans C, Chen T, Jonkers J, van Steensel B (2018) Easy quantification of template-directed CRISPR/Cas9 editing. Nucleic Acids Res 46(10):e58. https://doi.org/10.1093/nar/gky164
Bui HT, Van Thuan N, Wakayama T, Miyano T (2006) Chromatin remodeling in somatic cells injected into mature pig oocytes. Reproduction 131(6):1037–1049. https://doi.org/10.1530/rep.1.00897
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
Canovas S, Ivanova E, Romar R, Garcia-Martinez S, Soriano-Ubeda C, Garcia-Vazquez FA, Saadeh H, Andrews S, Kelsey G, Coy P (2017) DNA methylation and gene expression changes derived from assisted reproductive technologies can be decreased by reproductive fluids. eLife 6:e23670. doi:https://doi.org/10.7554/eLife.23670
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 U S A 109(43):17382–17387. https://doi.org/10.1073/pnas.1211446109
Chen F, Wang Y, Yuan Y, Zhang W, Ren Z, Jin Y, Liu X, Xiong Q, Chen Q, Zhang M, Li X, Zhao L, Li Z, Wu Z, Zhang Y, Hu F, Huang J, Li R, Dai Y (2015) Generation of B cell- deficient pigs by highly efficient CRISPR/Cas9-mediated gene targeting. J Genet Genom Yi chuan xue bao 42(8):437–444. https://doi.org/10.1016/j.jgg.2015.05.002
Chen S, Lee B, Lee AY, Modzelewski AJ, He L (2016) Highly Efficient Mouse Genome Editing by CRISPR Ribonucleoprotein Electroporation of Zygotes. J Biol Chem 291 (28):14457- 14467. https://doi.org/10.1074/jbc.M116.733154
Chen B, Gu P, Jia J, Liu W, Liu Y, Liu W, Xu T, Lin X, Lin T, Liu Y, Chen H, Xu M, Yuan J, Zhang J, Zhang Y, Xiao D, Gu W (2019a) Optimization strategy for generating gene- edited tibet minipigs by synchronized oestrus and cytoplasmic microinjection. Int J Biol Sci 15(12):2719–2732. https://doi.org/10.7150/ijbs.35930
Chen J, Wang H, Bai J, Liu W, Liu X, Yu D, Feng T, Sun Z, Zhang L, Ma L, Hu Y, Zou Y, Tan T, Zhong J, Hu M, Bai X, Pan D, Xing Y, Zhao Y, Tian K, Hu X, Li N (2019b) Generation of Pigs Resistant to Highly Pathogenic-Porcine Reproductive and Respiratory Syndrome Virus through Gene Editing of CD163. Int J Biol Sci 15(2):481–492. https://doi.org/10.7150/ijbs.25862
Chen J, An B, Yu B, Peng X, Yuan H, Yang Q, Chen X, Yu T, Wang L, Zhang X, Wang H, Zou X, Pang D, Ouyang H, Tang X (2020) CRISPR/Cas9-mediated knockin of human factor IX into swine factor IX locus effectively alleviates bleeding in hemophilia B pigs. Haematologica. https://doi.org/10.3324/haematol.2019.224063
Cho B, Kim SJ, Lee EJ, Ahn SM, Lee JS, Ji DY, Lee K, Kang JT (2018) Generation of insulin- deficient piglets by disrupting INS gene using CRISPR/Cas9 system. Transgenic Res 27(3):289–300. https://doi.org/10.1007/s11248-018-0074-1
Christian M, Cermak T, Doyle EL, Schmidt C, Zhang F, Hummel A, Bogdanove AJ, Voytas DF (2010) Targeting DNA double-strand breaks with TAL effector nucleases. Genetics 186(2):757–761. https://doi.org/10.1534/genetics.110.120717
Chuang CK, Chen CH, Huang CL, Su YH, Peng SH, Lin TY, Tai HC, Yang TS, Tu CF (2017) Generation of GGTA1 mutant pigs by direct pronuclear microinjection of CRISPR/Cas9 plasmid vectors. Anim Biotechnol 28(3):174–181. https://doi.org/10.1080/10495398.2016.1246453
Clark JL (2015) Killing the enviropigs. J Anim Ethics 5(1):20–30
Clifford H (2014) AquAdvantage® Salmon - a pioneering application of biotechnology in aquaculture. BMC Proc 8(S4):O31. https://doi.org/10.1186/1753-6561-8-s4-o31
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
Crociara P, Chieppa MN, Vallino Costassa E, Berrone E, Gallo M, Lo Faro M, Pintore MD, Iulini B, D'Angelo A, Perona G, Botter A, Formicola D, Rainoldi A, Paulis M, Vezzoni P, Meli F, Peverali FA, Bendotti C, Trolese MC, Pasetto L, Bonetto V, Lazzari G, Duchi R, Perota A, Lagutina I, Quadalti C, Gennero MS, Dezzutto D, Desiato R, Boido M, Ghibaudi M, Valentini MC, Caramelli M, Galli C, Casalone C, Corona C (2019) Motor neuron degeneration, severe myopathy and TDP-43 increase in a transgenic pig model of SOD1- linked familiar ALS. Neurobiol Dis 124:263–275. https://doi.org/10.1016/j.nbd.2018.11.021
Dai Y, Vaught TD, Boone J, Chen SH, Phelps CJ, Ball S, Monahan JA, Jobst PM, McCreath KJ, Lamborn AE, Cowell-Lucero JL, Wells KD, Colman A, Polejaeva IA, Ayares DL (2002) Targeted disruption of the alpha1,3-galactosyltransferase gene in cloned pigs. Nat Biotechnol 20(3):251–255. https://doi.org/10.1038/nbt0302-251
Dang-Nguyen TQ, Nguyen HT, Somfai T, Wells D, Men NT, Viet-Linh N, Noguchi J, Kaneko H, Kikuchi K, Nagai T (2018) Sucrose assists selection of high-quality oocytes in pigs. Anim Sci J Nihon chikusan Gakkaiho 89(6):880–887. https://doi.org/10.1111/asj.13015
Das S, Koyano-Nakagawa N, Gafni O, Maeng G, Singh BN, Rasmussen T, Pan X, Choi KD, Mickelson D, Gong W, Pota P, Weaver CV, Kren S, Hanna JH, Yannopoulos D, Garry MG, Garry DJ (2020) Generation of human endothelium in pig embryos deficient in ETV2. Nat Biotechnol 38(3):297–302. https://doi.org/10.1038/s41587-019-0373-y
Dehairs J, Talebi A, Cherifi Y, Swinnen JV (2016) CRISP-ID: decoding CRISPR mediated indels by Sanger sequencing. Scientific reports 6(1):28973. https://doi.org/10.1038/srep28973
Diao YF, Naruse KJ, Han RX, Li XX, Oqani RK, Lin T, Jin DI (2013) Treatment of fetal fibroblasts with DNA methylation inhibitors and/or histone deacetylase inhibitors improves the development of porcine nuclear transfer-derived embryos. Anim Reprod Sci 141(3-4):164–171. https://doi.org/10.1016/j.anireprosci.2013.08.008
Dorado B, Ploen GG, Barettino A, Macias A, Gonzalo P, Andres-Manzano MJ, Gonzalez-Gomez C, Galan-Arriola C, Alfonso JM, Lobo M, Lopez-Martin GJ, Molina A, Sanchez-Sanchez R, Gadea J, Sanchez-Gonzalez J, Liu Y, Callesen H, Filgueiras-Rama D, Ibanez B, Sorensen CB, Andres V (2019) Generation and characterization of a novel knockin minipig model of Hutchinson-Gilford progeria syndrome. Cell Discov 5(1):16. https://doi.org/10.1038/s41421-019-0084-z
Du Y, Kragh PM, Zhang Y, Li J, Schmidt M, Bogh IB, Zhang X, Purup S, Jorgensen AL, Pedersen AM, Villemoes K, Yang H, Bolund L, Vajta G (2007) Piglets born from handmade cloning, an innovative cloning method without micromanipulation. Theriogenology 68(8):1104–1110. https://doi.org/10.1016/j.theriogenology.2007.07.021
Dziuk P (1985) Effect of migration, distribution and spacing of pig embryos on pregnancy and fetal survival. J Reprod Fertil Suppl 33:57–63
Eid A, Alshareef S, Mahfouz MM (2018) CRISPR base editors: genome editing without double- stranded breaks. Biochem J 475(11):1955–1964. https://doi.org/10.1042/bcj20170793
Elkhadragy L, Regan MR, W MT, Goli KD, Patel S, Garcia K, Stewart M, Schook LB, Gaba RC, Schachtschneider KM (2021) Generation of genetically tailored porcine liver cancer cells by CRISPR/Cas9 editing. Biotechniques 70(1):37–48. https://doi.org/10.2144/btn-2020-0119
EMA (2001) Note for guidance on the quality, preclinical and clinical aspects of gene transfer medicinal products. European Medicines Agency (EMA), London
EMA (2006) Guideline on environmental risk assessments for medicinal products consisting of, or containing, genetically modified organisms (GMOs). European Medicines Agency (EMA), London
EMA (2009) Guideline on xenogeneic cell-based medicinal products. European Medicines Agency (EMA), London
EMA (2013) Guideline on Quality of biological active substances produced by transgene expression in animals. European Medicines Agency (EMA), London
EMA (2015) Kanuma sebelipase alfa European Medicines Agency (EMA)
EMA (2019) ATryn. Withdrawal of the marketing authorisation in the European Union EMA (2020) Ruconest conestat alfa European Medicines Agency (EMA)
Fajrial AK, He QQ, Wirusanti NI, Slansky JE, Ding X (2020) A review of emerging physical transfection methods for CRISPR/Cas9-mediated gene editing. Theranostics 10(12):5532–5549. https://doi.org/10.7150/thno.43465
FAO (2020) Food outlook biannual report on global food markets – June 2020. Food Outlook, Rome. https://doi.org/10.4060/ca9509en
FDA (2017) Guidance for industry regulation of intentionally altered genomic DNA in animals
FDA (2020) GalSafe pig. NADA 141-542. US Food & Drug Administration.
Feng J, Yang F (2019) The Regulation of Genetically Modified Food in China. Biotechnol Law Report 38(5):289–293. https://doi.org/10.1089/blr.2019.29137.jf
Fischer K, Rieblinger B, Hein R, Sfriso R, Zuber J, Fischer A, Klinger B, Liang W, Flisikowski K, Kurome M, Zakhartchenko V, Kessler B, Wolf E, Rieben R, Schwinzer R, Kind A, Schnieke A (2020) Viable pigs after simultaneous inactivation of porcine MHC class I and three xenoreactive antigen genes GGTA1, CMAH and B4GALNT2. Xenotransplantation 27(1):e12560. https://doi.org/10.1111/xen.12560
Forsberg CW, Meidinger RG, Liu M, Cottrill M, Golovan S, Phillips JP (2013) Integration, stability and expression of the E. coli phytase transgene in the Cassie line of Yorkshire Enviropig. Transgenic Res 22(2):379–389. https://doi.org/10.1007/s11248-012-9646-7
Forsberg CW, Meidinger RG, Ajakaiye A, Murray D, Fan MZ, Mandell IB, Phillips JP (2014a) Comparative carcass and tissue nutrient composition of transgenic Yorkshire pigs expressing phytase in the saliva and conventional Yorkshire pigs. J Anim Sci 92 (10):4417–4439. https://doi.org/10.2527/jas.2014-7780
Forsberg CW, Meidinger RG, Murray D, Keirstead ND, Hayes MA, Fan MZ, Ganeshapillai J, Monteiro MA, Golovan SP, Phillips JP (2014b) Phytase properties and locations in tissues of transgenic pigs secreting phytase in the saliva. J Anim Sci 92(8):3375–3387. https://doi.org/10.2527/jas.2014-7782
Fu R, Fang M, Xu K, Ren J, Zou J, Su L, Chen X, An P, Yu D, Ka M, Hai T, Li Z, Li W, Yang Y, Zhou Q, Hu Z (2020) Generation of GGTA1−/−β2M−/−CIITA−/− Pigs Using CRISPR/Cas9 technology to alleviate xenogeneic immune reactions. Transplantation 104(8):1566–1573. https://doi.org/10.1097/tp.0000000000003205
Gadea J, Garcia Vazquez F (2010) Applications of transgenic pigs in biomedicine and animal production. Itea-Informacion Tecnica Economica Agraria 106(1):30–45
Gadea J, Garcia-Vazquez FA, Hachem A, Bassett A, Romero-Aguirregomezcorta J, Canovas S, Romar R, Parrington J (2018) Generation of TPC2 knock out pig embryos by CRISPR- Cas technology. Reprod Domest Anim 53:87–88
Gao QS, Xuan MF, Luo ZB, Paek HJ, Kang JD, Yin XJ (2019) Hairless-knockout piglets generated using the clustered regularly interspaced short palindromic repeat/CRISPR- associated-9 exhibit abnormalities in the skin and thymus. Exp Anim 68(4):519–529. https://doi.org/10.1538/expanim.19-0018
Garcia-Vazquez FA, Ruiz S, Matas C, Izquierdo-Rico MJ, Grullon LA, De Ondiz A, Vieira L, Aviles-Lopez K, Gutierrez-Adan A, Gadea J (2010) Production of transgenic piglets using ICSI-sperm-mediated gene transfer in combination with recombinase RecA. Reproduction 140(2):259–272. https://doi.org/10.1530/REP-10-0129
Garcia-Vazquez FA, Hernandez-Caravaca I, Martin M, Gomez E, Rodriguez A, Sanchez-Sanchez R, Gadea J (2011) Two cases of reciprocal chromosomal translocation (4; 7)(p+; q-) (2; 8)(q-; q+) in piglets produced by ICSI. Reprod Domes Anim 46(4):728–730. https://doi.org/10.1111/j.1439-0531.2010.01707.x
Giuffra E, Kijas JM, Amarger V, Carlborg O, Jeon JT, Andersson L (2000) The origin of the domestic pig: independent domestication and subsequent introgression. Genetics 154(4):1785–1791
Golovan SP, Meidinger RG, Ajakaiye A, Cottrill M, Wiederkehr MZ, Barney DJ, Plante C, Pollard JW, Fan MZ, Hayes MA, Laursen J, Hjorth JP, Hacker RR, Phillips JP, Forsberg CW (2001) Pigs expressing salivary phytase produce low-phosphorus manure. Nat Biotechnol 19(8):741–745. https://doi.org/10.1038/90788
Golovan SP, Hakimov HA, Verschoor CP, Walters S, Gadish M, Elsik C, Schenkel F, Chiu DK, Forsberg CW (2008) Analysis of Sus scrofa liver proteome and identification of proteins differentially expressed between genders, and conventional and genetically enhanced lines. Comparative biochemistry and physiology Part D, Genomics & proteomics 3(3):234–242. https://doi.org/10.1016/j.cbd.2008.05.001
Gordon JW, Ruddle FH (1981) Integration and stable germ line transmission of genes injected into mouse pronuclei. Science 214(4526):1244–1246. https://doi.org/10.1126/science.6272397
Gordon JW, Scangos GA, Plotkin DJ, Barbosa JA, Ruddle FH (1980) Genetic transformation of mouse embryos by microinjection of purified DNA. Proc Natl Acad Sci U S A 77(12):7380–7384. https://doi.org/10.1073/pnas.77.12.7380
Guo C, Wang M, Zhu Z, He S, Liu H, Liu X, Shi X, Tang T, Yu P, Zeng J, Yang L, Cao Y, Chen Y, Liu X, He Z (2019a) Highly Efficient Generation of Pigs Harboring a Partial Deletion of the CD163 SRCR5 Domain, Which Are Fully Resistant to Porcine Reproductive and Respiratory Syndrome Virus 2 Infection. Front Immunol 10 (1846):1846. doi:https://doi.org/10.3389/fimmu.2019.01846
Guo Z, Lv L, Lui D, Fu B (2019b) Delayed activation methods and development of pig somatic cell nuclear transfer embryos: a meta-analysis. Large Anim Rev 25(2):69–73
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. https://doi.org/10.1038/cr.2014.11
Hai T, Guo W, Yao J, Cao C, Luo A, Qi M, Wang X, Wang X, Huang J, Zhang Y, Zhang H, Wang D, Shang H, Hong Q, Zhang R, Jia Q, Zheng Q, Qin G, Li Y, Zhang T, Jin W, Chen ZY, Wang H, Zhou Q, Meng A, Wei H, Yang S, Zhao J (2017) Creation of miniature pig model of human Waardenburg syndrome type 2A by ENU mutagenesis. Hum Genet 136(11-12):1463–1475. https://doi.org/10.1007/s00439-017-1851-2
Hammer RE, Pursel VG, Rexroad CE Jr, Wall RJ, Bolt DJ, Ebert KM, Palmiter RD, Brinster RL (1985) Production of transgenic rabbits, sheep and pigs by microinjection. Nature 315(6021):680–683. https://doi.org/10.1038/315680a0
Han X, Gao Y, Li G, Xiong Y, Zhao C, Ruan J, Ma Y, Li X, Li C, Zhao S, Xie S (2020) Enhancing the antibacterial activities of sow milk via site-specific knock-in of a lactoferrin gene in pigs using CRISPR/Cas9 technology. Cell Biosci 10(1):133. https://doi.org/10.1186/s13578-020-00496-y
Hatada L (2017) Genome editing in animals, vol 1630. Methods in molecular biology. Springer New York, New York. https://doi.org/10.1007/978-1-4939-7128-2
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 U S A 108(29):12013–12017. https://doi.org/10.1073/pnas.1106422108
He Q, Yu D, Bao M, Korensky G, Chen J, Shin M, Kim J, Park M, Qin P, Du K (2020) High- throughput and all-solution phase African Swine Fever Virus (ASFV) detection using CRISPR-Cas12a and fluorescence based point-of-care system. Biosens Bioelectron 154:112068. https://doi.org/10.1016/j.bios.2020.112068
Hein R, Sake HJ, Pokoyski C, Hundrieser J, Brinkmann A, Baars W, Nowak-Imialek M, Lucas-Hahn A, Figueiredo C, Schuberth HJ, Niemann H, Petersen B, Schwinzer R (2020) Triple (GGTA1, CMAH, B2M) modified pigs expressing an SLA class I(low) phenotype- Effects on immune status and susceptibility to human immune responses. Am J Transplant 20(4):988–998. https://doi.org/10.1111/ajt.15710
Hinrichs A, Kessler B, Kurome M, Blutke A, Kemter E, Bernau M, Scholz AM, Rathkolb B, Renner S, Bultmann S, Leonhardt H, de Angelis MH, Nagashima H, Hoeflich A, Blum WF, Bidlingmaier M, Wanke R, Dahlhoff M, Wolf E (2018) Growth hormone receptor- deficient pigs resemble the pathophysiology of human Laron syndrome and reveal altered activation of signaling cascades in the liver. Molecular metabolism 11:113–128. https://doi.org/10.1016/j.molmet.2018.03.006
Hinrichs A, Riedel EO, Klymiuk N, Blutke A, Kemter E, Langin M, Dahlhoff M, Kessler B, Kurome M, Zakhartchenko V, Jemiller EM, Ayares D, Bidlingmaier M, Flenkenthaler F, Hrabe de Angelis M, Arnold GJ, Reichart B, Frohlich T, Wolf E (2020) Growth hormone receptor knockout to reduce the size of donor pigs for preclinical xenotransplantation studies. Xenotransplantation n/a (n/a):e12664. https://doi.org/10.1111/xen.12664
Hirata M, Tanihara F, Wittayarat M, Hirano T, Nguyen NT, Le QA, Namula Z, Nii M, Otoi T (2019) Genome mutation after introduction of the gene editing by electroporation of Cas9 protein (GEEP) system in matured oocytes and putative zygotes. Vitro Cell Dev Biol Anim 55(4):237–242. https://doi.org/10.1007/s11626-019-00338-3
Hirata M, Wittayarat M, Tanihara F, Sato Y, Namula Z, Le QA, Lin Q, Takebayashi K, Otoi T (2020) One-step genome editing of porcine zygotes through the electroporation of a CRISPR/Cas9 system with two guide RNAs. In Vitro Cell Dev Biol Anim 56 (8):614–621. https://doi.org/10.1007/s11626-020-00507-9
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. https://doi.org/10.1038/nbt.1927
Hofmann A, Kessler B, Ewerling S, Weppert M, Vogg B, Ludwig H, Stojkovic M, Boelhauve M, Brem G, Wolf E, Pfeifer A (2003) Efficient transgenesis in farm animals by lentiviral vectors. EMBO Rep 4(11):1054–1060. https://doi.org/10.1038/sj.embor.embor7400007
Hooper M, Hardy K, Handyside A, Hunter S, Monk M (1987) HPRT-deficient (Lesch-Nyhan) mouse embryos derived from germline colonization by cultured cells. Nature 326(6110):292–295. https://doi.org/10.1038/326292a0
Hornak M, Hulinska P, Musilova P, Kubickova S, Rubes J (2009) Investigation of chromosome aneuploidies in early porcine embryos using comparative genomic hybridization. Cytogenet Genome Res 126(1-2):210–216. https://doi.org/10.1159/000245922
Hryhorowicz M, Lipinski D, Hryhorowicz S, Nowak-Terpilowska A, Ryczek N, Zeyland J (2020) Application of genetically engineered pigs in biomedical research. Genes (Basel) 11(6):670. https://doi.org/10.3390/genes11060670
Hu S, Qiao J, Fu Q, Chen C, Ni W, Wujiafu S, Ma S, Zhang H, Sheng J, Wang P, Wang D, Huang J, Cao L, Ouyang H (2015) Transgenic shRNA pigs reduce susceptibility to foot and mouth disease virus infection. eLife 4:e06951. https://doi.org/10.7554/eLife.06951
Huan YJ, Zhu J, Xie BT, Wang JY, Liu SC, Zhou Y, Kong QR, He HB, Liu ZH (2013) Treating cloned embryos, but not donor cells, with 5-aza-2′-deoxycytidine enhances the developmental competence of porcine cloned embryos. J Reprod Dev 59(5):442–449. https://doi.org/10.1262/jrd.2013-026
Huang L, Hua Z, Xiao H, Cheng Y, Xu K, Gao Q, Xia Y, Liu Y, Zhang X, Zheng X, Mu Y, Li K (2017) CRISPR/Cas9-mediated ApoE -/- and LDLR -/- double gene knockout in pigs elevates serum LDL-C and TC levels. Oncotarget 8(23)
Huang J, Wang A, Huang C, Sun Y, Song B, Zhou R, Li L (2020a) Generation of marker-free pbd-2 knock-in pigs using the CRISPR/Cas9 and Cre/loxP systems. Genes (Basel) 11(8):1–14. https://doi.org/10.3390/genes11080951
Huang X, Zou X, Xu Z, Tang F, Shi J, Zheng E, Liu D, Moisyadi S, Urschitz J, Wu Z, Li Z (2020b) Efficient deletion of LoxP-flanked selectable marker genes from the genome of transgenic pigs by an engineered Cre recombinase. Transgenic Res 29(3):307–319. https://doi.org/10.1007/s11248-020-00200-3
Hubner A, Petersen B, Keil GM, Niemann H, Mettenleiter TC, Fuchs W (2018) Efficient inhibition of African swine fever virus replication by CRISPR/Cas9 targeting of the viral p30 gene (CP204L). Scientific Rep 8(1):1449. https://doi.org/10.1038/s41598-018-19626-1
Hunter RHF, Polge C, Rowson LE (1967) The recovery, transfer and survival of blastocysts in pigs. J Reprod Fertil 14(3):501–502
Hwang SU, Eun K, Yoon JD, Kim H, Hyun SH (2018) Production of transgenic pigs using a pGFAP-CreER(T2)/EGFP (LoxP) inducible system for central nervous system disease models. J Vet Sci 19(3):434–445. https://doi.org/10.4142/jvs.2018.19.3.434
Im GS, Lai L, Liu Z, Hao Y, Wax D, Bonk A, Prather RS (2004) In vitro development of preimplantation porcine nuclear transfer embryos cultured in different media and gas atmospheres. Theriogenology 61(6):1125–1135. https://doi.org/10.1016/j.theriogenology.2003.06.006
Jeong YS, Yeo S, Park JS, Lee KK, Kang YK (2007) Gradual development of a genome-wide H3-K9 trimethylation pattern in paternally derived pig pronucleus. Dev Dyn 236(6):1509–1516. https://doi.org/10.1002/dvdy.21150
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
Kang JT, Ryu J, Cho B, Lee EJ, Yun YJ, Ahn S, Lee J, Ji DY, Lee K, Park KW (2016) Generation of RUNX3 knockout pigs using CRISPR/Cas9-mediated gene targeting. Reprod Domes Anim 51(6):970–978. https://doi.org/10.1111/rda.12775
Kang J-D, Kim S, Zhu H-Y, Jin L, Guo Q, Li X-C, Zhang Y-C, Xing X-X, Xuan M-F, Zhang G-L, Luo Q-R, Kim YS, Cui C-D, Li W-X, Cui Z-Y, Kim J-S, Yin X-J (2017) Generation of cloned adult muscular pigs with myostatin gene mutation by genetic engineering. RSC Adv 7(21):12541–12549. https://doi.org/10.1039/c6ra28579a
Kikuchi K, Onishi A, Kashiwazaki N, Iwamoto M, Noguchi J, Kaneko H, Akita T, Nagai T (2002) Successful piglet production after transfer of blastocysts produced by a modified in vitro system. Biol Reprod 66(4):1033–1041
Kim YB, Komor AC, Levy JM, Packer MS, Zhao KT, Liu DR (2017) Increasing the genome- targeting scope and precision of base editing with engineered Cas9-cytidine deaminase fusions. Nat Biotechnol 35(4):371–376. https://doi.org/10.1038/nbt.3803
Koblan LW, Doman JL, Wilson C, Levy JM, Tay T, Newby GA, Maianti JP, Raguram A, Liu DR (2018) Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction. Nat Biotechnol 36(9):843–846. https://doi.org/10.1038/nbt.4172
Koketsu Y, Tani S, Iida R (2017) Factors for improving reproductive performance of sows and herd productivity in commercial breeding herds. Porcine Health Manag 3:1. https://doi.org/10.1186/s40813-016-0049-7
Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR (2016) Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533(7603):420–424. https://doi.org/10.1038/nature17946
Komor AC, Zhao KT, Packer MS, Gaudelli NM, Waterbury AL, Koblan LW, Kim YB, Badran AH, Liu DR (2017) Improved base excision repair inhibition and bacteriophage Mu Gam protein yields C:G-to-T:A base editors with higher efficiency and product purity. Sci Adv 3 (8):eaao4774. https://doi.org/10.1126/sciadv.aao4774
Koppes EA, Redel BK, Johnson MA, Skvorak KJ, Ghaloul-Gonzalez L, Yates ME, Lewis DW, Gollin SM, Wu YL, Christ SE, Yerle M, Leshinski A, Spate LD, Benne JA, Murphy SL, Samuel MS, Walters EM, Hansen SA, Wells KD, Lichter-Konecki U, Wagner RA, Newsome JT, Dobrowolski SF, Vockley J, Prather RS, Nicholls RD (2020) A porcine model of phenylketonuria generated by CRISPR/Cas9 genome editing. JCI Insight 5(20). https://doi.org/10.1172/jci.insight.141523
Kumar BM, Maeng GH, Lee YM, Lee JH, Jeon BG, Ock SA, Kang T, Rho GJ (2013) Epigenetic modification of fetal fibroblasts improves developmental competency and gene expression in porcine cloned embryos. Vet Res Commun 37(1):19–28. https://doi.org/10.1007/s11259-012-9542-x
Kurome M, Kessler B, Wuensch A, Nagashima H, Wolf E (2015) Nuclear transfer and transgenesis in the pig. In: N., H., A. (eds) Nuclear reprogramming. Methods in molecular biology, vol 1222. Methods and protocols. Humana Press, New York, pp 37–59. https://doi.org/10.1007/978-1-4939-1594-1_4
Kurtz S, Lucas-Hahn A, Schlegelberger B, Gohring G, Niemann H, Mettenleiter TC, Petersen B (2021) Knockout of the HMG domain of the porcine SRY gene causes sex reversal in gene-edited pigs. Proc Natl Acad Sci U S A 118(2). https://doi.org/10.1073/pnas.2008743118
Kwon J, Namgoong S, Kim NH (2015) CRISPR/Cas9 as tool for functional study of genes involved in preimplantation embryo development. PLoS One 10(3):e0120501. https://doi.org/10.1371/journal.pone.0120501
Lai L, Kolber-Simonds D, Park KW, Cheong HT, Greenstein JL, Im GS, Samuel M, Bonk A, Rieke A, Day BN, Murphy CN, Carter DB, Hawley RJ, Prather RS (2002) Production of alpha-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning. Science 295(5557):1089–1092. https://doi.org/10.1126/science.1068228
Lai S, Wei S, Zhao B, Ouyang Z, Zhang Q, Fan N, Liu Z, Zhao Y, Yan Q, Zhou X, Li L, Xin J, Zeng Y, Lai L, Zou Q (2016) Generation of knock-in pigs carrying Oct4-tdTomato reporter through CRISPR/Cas9-mediated genome engineering. PLoS One 11 (1):e0146562. https://doi.org/10.1371/journal.pone.0146562
Lamas-Toranzo I, Guerrero-Sanchez J, Miralles-Bover H, Alegre-Cid G, Pericuesta E, Bermejo-Alvarez P (2017) CRISPR is knocking on barn door. Reprod Domes Anim 52 Suppl 4:39–47. https://doi.org/10.1111/rda.13047
Lamas-Toranzo I, Fonseca Balvis N, Querejeta-Fernandez A, Izquierdo-Rico MJ, Gonzalez-Brusi L, Lorenzo PL, Garcia-Rebollar P, Aviles M, Bermejo-Alvarez P (2019a) ZP4 confers structural properties to the zona pellucida essential for embryo development. eLife 8:e48904. doi:https://doi.org/10.7554/eLife.48904
Lamas-Toranzo I, Galiano-Cogolludo B, Cornudella-Ardiaca F, Cobos-Figueroa J, Ousinde O, Bermejo-Alvarez P (2019b) Strategies to reduce genetic mosaicism following CRISPR- mediated genome edition in bovine embryos. Scientific reports 9(1):14900. https://doi.org/10.1038/s41598-019-51366-8
Lassnig C, Müller M (2015) Disease-resistant transgenic animals. In: Meyers (ed) Encyclopedia of sustainability science and technology. Springer New York, New York, pp 1–17. https://doi.org/10.1007/978-1-4939-2493-6_10-3
Lavitrano M, Forni M, Varzi V, Pucci L, Bacci ML, Di Stefano C, Fioretti D, Zoraqi G, Moioli B, Rossi M, Lazzereschi D, Stoppacciaro A, Seren E, Alfani D, Cortesini R, Frati L (1997) Sperm-mediated gene transfer: production of pigs transgenic for a human regulator of complement activation. Transplant Proc 29(8):3508–3509. https://doi.org/10.1016/s0041-1345(97)00998-6
Le QA, Hirata M, Nguyen NT, Takebayashi K, Wittayarat M, Sato Y, Namula Z, Nii M, Tanihara F, Otoi T (2020) Effects of electroporation treatment using different concentrations of Cas9 protein with gRNA targeting Myostatin (MSTN) genes on the development and gene editing of porcine zygotes. Anim Sci J Nihon chikusan Gakkaiho 91 (1):e13386. https://doi.org/10.1111/asj.13386
Lee K, Prather RS (2014) Cloning pigs by somatic cell nuclear transfer. In: Cibelli, Gurdon, Wilmut et al. (eds) Principles of cloning, 2nd edn. Academic, San Diego, pp 245–254. https://doi.org/10.1016/B978-0-12-386541-0.00019-9
Legge M (1995) Oocyte and zygote zona pellucida permeability to macromolecules. J Exp Zool 271(2):145–150. https://doi.org/10.1002/jez.1402710210
Li J, Rieke A, Day BN, Prather RS (1996) Technical note: porcine non-surgical embryo transfer. J Anim Sci 74 (9):2263–2268. https://doi.org/10.2527/1996.7492263x
Li L, Pang D, Wang T, Li Z, Chen L, Zhang M, Song N, Nie D, Chen Z, Lai L, Ouyang H (2009) Production of a reporter transgenic pig for monitoring Cre recombinase activity. Biochem Biophys Res Commun 382(2):232–235. https://doi.org/10.1016/j.bbrc.2009.02.146
Li S, Flisikowska T, Kurome M, Zakhartchenko V, Kessler B, Saur D, Kind A, Wolf E, Flisikowski K, Schnieke A (2014) Dual fluorescent reporter pig for Cre recombination: transgene placement at the ROSA26 locus. PLoS One 9(7):e102455. https://doi.org/10.1371/journal.pone.0102455
Li P, Estrada JL, Burlak C, Montgomery J, Butler JR, Santos RM, Wang ZY, Paris LL, Blankenship RL, Downey SM, Tector M, Tector AJ (2015) Efficient generation of genetically distinct pigs in a single pregnancy using multiplexed single-guide RNA and carbohydrate selection. Xenotransplantation 22(1):20–31. https://doi.org/10.1111/xen.12131
Li G, Zhang X, Zhong C, Mo J, Quan R, Yang J, Liu D, Li Z, Yang H, Wu Z (2017a) Small molecules enhance CRISPR/Cas9-mediated homology-directed genome editing in primary cells. Scientific Rep 7(1):8943. https://doi.org/10.1038/s41598-017-09306-x
Li Z, Yang HY, Wang Y, Zhang ML, Liu XR, Xiong Q, Zhang LN, Jin Y, Mou LS, Liu Y, Li RF, Rao Y, Dai YF (2017b) Generation of tryptophan hydroxylase 2 gene knockout pigs by CRISPR/Cas9-mediated gene targeting. Journal of biomedical research 31 (5):445- 452. https://doi.org/10.7555/JBR.31.20170026
Li M, Ouyang H, Yuan H, Li J, Xie Z, Wang K, Yu T, Liu M, Chen X, Tang X, Jiao H, Pang D (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
Li L, Meng H, Zou Q, Zhang J, Cai L, Yang B, Weng J, Lai L, Yang H, Gao Y (2019a) Establishment of gene-edited pigs expressing human blood-coagulation factor VII and albumin for bioartificial liver use. J Gastroenterol Hepatol 34(10):1851–1859. https://doi.org/10.1111/jgh.14666
Li R, Miao J, Wang Z (2019b) Production of genetically engineered porcine embryos by handmade cloning. Methods Mol Biol 1874:347–360. https://doi.org/10.1007/978-1-4939-8831-0_20
Li G, Zhang X, Wang H, Mo J, Zhong C, Shi J, Zhou R, Li Z, Yang H, Wu Z, Liu D (2020a) CRISPR/Cas9-Mediated Integration of Large Transgene into Pig CEP112 Locus. G3 (Bethesda, Md) 10(2):467–473. https://doi.org/10.1534/g3.119.400810
Li R, Zeng W, Ma M, Wei Z, Liu H, Liu X, Wang M, Shi X, Zeng J, Yang L, Mo D, Liu X, Chen Y, He Z (2020b) Precise editing of myostatin signal peptide by CRISPR/Cas9 increases the muscle mass of Liang Guang Small Spotted pigs. Transgenic Res 29 (1):149–163. https://doi.org/10.1007/s11248-020-00188-w
Li W, Shi L, Zhuang Z, Wu H, Lian M, Chen Y, Li L, Ge W, Jin Q, Zhang Q, Zhao Y, Liu Z, Ouyang Z, Ye Y, Li Y, Wang H, Liao Y, Quan L, Xiao L, Lai L, Meng G, Wang K (2020c) Engineered Pigs Carrying a Gain-of-Function NLRP3 Homozygous Mutation Can Survive to Adulthood and Accurately Recapitulate Human Systemic Spontaneous Inflammatory Responses. J Immunol 205(9):2532–2544. https://doi.org/10.4049/jimmunol.1901468
Liu L, Lee C, Moor RM (1996) DNA synthesis, microtubule and nuclear dynamics in porcine parthenotes. Zygote 4(2):139–144. https://doi.org/10.1017/s0967199400003014
Liu L, Liu Y, Gao F, Song G, Wen J, Guan J, Yin Y, Ma X, Tang B, Li Z (2012) Embryonic development and gene expression of porcine SCNT embryos treated with sodium butyrate. J Exp Zool B Mol Dev Evol 318(3):224–234. https://doi.org/10.1002/jez.b.22440
Liu T, Dou H, Xiang X, Li L, Li Y, Lin L, Pang X, Zhang Y, Chen Y, Luan J, Xu Y, Yang Z, Yang W, Liu H, Li F, Wang H, Yang H, Bolund L, Vajta G, Du Y (2015) Factors determining the efficiency of porcine somatic cell nuclear transfer: data analysis with over 200,000 reconstructed embryos. Cell Reprogram 17(6):463–471. https://doi.org/10.1089/cell.2015.0037
Liu Y, Lucas-Hahn A, Petersen B, Li R, Hermann D, Hassel P, Ziegler M, Larsen K, Niemann H, Callesen H (2017) Developmental competence and epigenetic profile of porcine embryos produced by two different cloning methods. Cell Reprogram 19(3):171–179. https://doi.org/10.1089/cell.2016.0055
Liu X, Liu H, Wang M, Li R, Zeng J, Mo D, Cong P, Liu X, Chen Y, He Z (2019) Disruption of the ZBED6 binding site in intron 3 of IGF2 by CRISPR/Cas9 leads to enhanced muscle development in Liang Guang Small Spotted pigs. Transgenic Res 28(1):141–150. https://doi.org/10.1007/s11248-018-0107-9
Luo W, Li Z, Huang Y, Han Y, Yao C, Duan X, Ouyang H, Li L (2014a) Generation of AQP2- Cre transgenic mini-pigs specifically expressing Cre recombinase in kidney collecting duct cells. Transgenic Res 23(2):365–375. https://doi.org/10.1007/s11248-013-9774-8
Luo W, Li Z, Li P, Huang Y, Han Y, Yao C, Zhang Z, Yan H, Pang D, Ouyang H, Li L (2014b) Expression of Cre recombinase in alveolar epithelial cells of the AQP2-Cre transgenic mini-pigs. Cell Physiol Biochem 34(5):1597–1613. https://doi.org/10.1159/000366363
Luo L, Wang S, Zhu L, Fan B, Liu T, Wang L, Zhao P, Dang Y, Sun P, Chen J, Zhang Y, Chang X, Yu Z, Wang H, Guo R, Li B, Zhang K (2019) Aminopeptidase N-null neonatal piglets are protected from transmissible gastroenteritis virus but not porcine epidemic diarrhea virus. Scientific Rep 9(1):13186. https://doi.org/10.1038/s41598-019-49838-y
Lv L, Lu X, Feng T, Rehman S, Sun J, Wu Z, Shi D, Liu Q, Cui K (2020) Valproic acid enhances in vitro developmental competence of porcine handmade cloned embryos. Livestock Science 233:103957. https://doi.org/10.1016/j.livsci.2020.103957
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. https://doi.org/10.1126/science.1232033
Mao J, Ajakaiye A, Lan Y, Olk DC, Ceballos M, Zhang T, Fan MZ, Forsberg CW (2008) Chemical structures of manure from conventional and phytase transgenic pigs investigated by advanced solid-state NMR spectroscopy. J Agric Food Chem 56(6):2131–2138. https://doi.org/10.1021/jf071588x
Marchal R, Feugang JM, Perreau C, Venturi E, Terqui M, Mermillod P (2001) Meiotic and developmental competence of prepubertal and adult swine oocytes. Theriogenology 56(1):17–29. https://doi.org/10.1016/s0093-691x(01)00539-8
Martinez EA, Martinez CA, Cambra JM, Maside C, Lucas X, Vazquez JL, Vazquez JM, Roca J, Rodriguez-Martinez H, Gil MA, Parrilla I, Cuello C (2019) Achievements and future perspectives of embryo transfer technology in pigs. Reprod Domes Anim 54 Suppl 4(S4):4–13. https://doi.org/10.1111/rda.13465
Martinez CA, Cambra JM, Gil MA, Parrilla I, Alvarez-Rodriguez M, Rodriguez-Martinez H, Cuello C, Martinez EA (2020) Seminal Plasma Induces Overexpression of Genes Associated with Embryo Development and Implantation in Day-6 Porcine Blastocysts. Int J Mol Sci 21 (10):3662. https://doi.org/10.3390/ijms21103662
McCreath KJ, Howcroft J, Campbell KH, Colman A, Schnieke AE, Kind AJ (2000) Production of gene-targeted sheep by nuclear transfer from cultured somatic cells. Nature 405(6790):1066–1069. https://doi.org/10.1038/35016604
Mehravar M, Shirazi A, Nazari M, Banan M (2019) Mosaicism in CRISPR/Cas9-mediated genome editing. Dev Biol 445(2):156–162. https://doi.org/10.1016/j.ydbio.2018.10.008
Miller JC, Holmes MC, Wang J, Guschin DY, Lee YL, Rupniewski I, Beausejour CM, Waite AJ, Wang NS, Kim KA, Gregory PD, Pabo CO, Rebar EJ (2007) An improved zinc-finger nuclease architecture for highly specific genome editing. Nat Biotechnol 25(7):778–785. https://doi.org/10.1038/nbt1319
Miyoshi K, Kawaguchi H, Maeda K, Sato M, Akioka K, Noguchi M, Horiuchi M, Tanimoto A (2016) Birth of cloned microminipigs derived from somatic cell nuclear transfer embryos that have been transiently treated with valproic acid. Cell Reprogram 18(6):390–400. https://doi.org/10.1089/cell.2016.0025
Mojica FJM, 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. vol 36. https://doi.org/10.1046/j.1365-2958.2000.01838.x
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
Moore FE, Reyon D, Sander JD, Martinez SA, Blackburn JS, Khayter C, Ramirez CL, Joung JK, Langenau DM (2012) Improved somatic mutagenesis in zebrafish using transcription activator-like effector nucleases (TALENs). PLoS One 7(5):e37877. https://doi.org/10.1371/journal.pone.0037877
Murray JD, Maga EA (2016) Genetically engineered livestock for agriculture: a generation after the first transgenic animal research conference. Transgenic Res 25(3):321–327. https://doi.org/10.1007/s11248-016-9927-7
Murray D, Meidinger RG, Golovan SP, Phillips JP, O'Halloran IP, Fan MZ, Hacker RR, Forsberg CW (2007) Transgene and mitochondrial DNA are indicators of efficient composting of transgenic pig carcasses. Bioresource technology 98(9):1795–1804. https://doi.org/10.1016/j.biortech.2006.06.029
Naeimi Kararoudi M, Hejazi SS, Elmas E, Hellstrom M, Naeimi Kararoudi M, Padma AM, Lee D, Dolatshad H (2018) Clustered regularly interspaced short palindromic repeats/Cas9 gene editing technique in xenotransplantation. Front Immunol 9:1711. https://doi.org/10.3389/fimmu.2018.01711
Navarro-Serna S, Romar R, Dehesa-Etxebeste M, Lopes JS, Lopez de Munain A, Gadea J (2019) First production of Calpain3 KO pig embryo by CRISPR/Cas9 technology for human disease modelling: efficiency comparison between electroporation and intracytoplasmic microinjection. In: 35rd Scientific meeting Association of Embryo Technology in Europe (AETE). Murcia (Spain). 13-14th September 2019
Navarro-Serna S, Vilarino M, Park I, Gadea J, Ross PJ (2020) Livestock gene editing by one- step embryo manipulation. J Equine Vet Sci 89:103025. https://doi.org/10.1016/j.jevs.2020.103025
Navarro-Serna S, Hachem A, Canha-Gouveia A, Hanbashi A, Garrappa G, Lopes JS, Paris-Oller E, Sarrias-Gil L, Flores-Flores C, Bassett A, Sanchez R, Bermejo-Alvarez P, Matas C, Romar R, Parrington J, Gadea J (2021) Generation of nonmosaic, two-pore channel 2 Biallelic knockout pigs in one generation by CRISPR-Cas9 microinjection before oocyte insemination. CRISPR J 4(1):132–146. https://doi.org/10.1089/crispr.2020.0078
Niemann H, Petersen B (2016) The production of multi-transgenic pigs: update and perspectives for xenotransplantation. Transgenic Res 25(3):361–374. https://doi.org/10.1007/s11248-016-9934-8
Nishio K, Tanihara F, Nguyen TV, Kunihara T, Nii M, Hirata M, Takemoto T, Otoi T (2018) Effects of voltage strength during electroporation on the development and quality of in vitro-produced porcine embryos. Reprod Domes Anim 53 (2):313–318. https://doi.org/10.1111/rda.13106
Niu D, Wei HJ, Lin L, George H, Wang T, Lee IH, Zhao HY, Wang Y, Kan Y, Shrock E, Lesha E, Wang G, Luo Y, Qing Y, Jiao D, Zhao H, Zhou X, Wang S, Wei H, Güell M, Church GM, Yang L (2017) Inactivation of porcine endogenous retrovirus in pigs using CRISPR- Cas9. Science 357(6357):1303–1307. https://doi.org/10.1126/science.aan4187
Niu D, Ma X, Yuan T, Niu Y, Xu Y, Sun Z, Ping Y, Li W, Zhang J, Wang T, Church GM (2021) Porcine genome engineering for xenotransplantation. Adv Drug Delivery Rev 168:229–245. https://doi.org/10.1016/j.addr.2020.04.001
Novoselova TA, Meuwissen MPM, Jongbloed AW, Huirne RBM (2013) Expected economic performance of genetic modification in pork production. NJAS Wageningen J Life Sci 64-65:9–15. https://doi.org/10.1016/j.njas.2012.03.002
Onishi A, Iwamoto M, Akita T, Mikawa S, Takeda K, Awata T, Hanada H, Perry AC (2000) Pig cloning by microinjection of fetal fibroblast nuclei. Science 289(5482):1188–1190. https://doi.org/10.1126/science.289.5482.1188
Ostedgaard LS, Price MP, Whitworth KM, Abou Alaiwa MH, Fischer AJ, Warrier A, Samuel M, Spate LD, Allen PD, Hilkin BM, Romano Ibarra GS, Ortiz Bezara ME, Goodell BJ, Mather SE, Powers LS, Stroik MR, Gansemer ND, Hippee CE, Zarei K, Goeken JA, Businga TR, Hoffman EA, Meyerholz DK, Prather RS, Stoltz DA, Welsh MJ (2020) Lack of airway submucosal glands impairs respiratory host defenses. eLife 9:e59653. doi:https://doi.org/10.7554/eLife.59653
Palmiter RD, Brinster RL, Hammer RE, Trumbauer ME, Rosenfeld MG, Birnberg NC, Evans RM (1982) Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes. Nature 300(5893):611–615. https://doi.org/10.1038/300611a0
Paris-Oller E, Navarro-Serna S, Soriano-Ubeda C, Lopes JS, Matas C, Ruiz S, Latorre R, Lopez-Albors O, Romar R, Canovas S, Coy P (2021) Reproductive fluids, used for the in vitro production of pig embryos, result in healthy offspring and avoid aberrant placental expression of PEG3 and LUM. J Anim Sci Biotechnol 12(1):32. https://doi.org/10.1186/s40104-020-00544-0
Park KW, Cheong HT, Lai LX, Im GS, Kuhholzer B, Bonk A, Samuel M, Rieke A, Day BN, Murphy CN, Carter DB, Prather RS (2001) Production of nuclear transfer-derived swine that express the enhanced green fluorescent protein. Animal Biotechnology 12(2):173–181
Park SJ, Park HJ, Koo OJ, Choi WJ, Moon JH, Kwon DK, Kang JT, Kim S, Choi JY, Jang G, Lee BC (2012) Oxamflatin improves developmental competence of porcine somatic cell nuclear transfer embryos. Cell Reprogram 14(5):398–406. https://doi.org/10.1089/cell.2012.0007
Park KE, Park CH, Powell A, Martin J, Donovan DM, Telugu BP (2016) Targeted gene knockin in porcine somatic cells using CRISPR/Cas ribonucleoproteins. Int J Mol Sci 17(6):810–810. https://doi.org/10.3390/ijms17060810
Park KE, Powell A, Sandmaier SE, Kim CM, Mileham A, Donovan DM, Telugu BP (2017) Targeted gene knock-in by CRISPR/Cas ribonucleoproteins in porcine zygotes. Scientific Rep 7:42458. https://doi.org/10.1038/srep42458
Peng J, Wang Y, Jiang J, Zhou X, Song L, Wang L, Ding C, Qin J, Liu L, Wang W, Liu J, Huang X, Wei H, Zhang P (2015) Production of human albumin in pigs through CRISPR/Cas9-mediated knockin of human cDNA into swine albumin locus in the zygotes. Scientific Rep 5:16705. https://doi.org/10.1038/srep16705
Perleberg C, Kind A, Schnieke A (2018) Genetically engineered pigs as models for human disease. Dis Models Mechan 11 (1):dmm030783. https://doi.org/10.1242/dmm.030783
Petersen B (2017) Basics of genome editing technology and its application in livestock species. Reprod Domes Anim 52 Suppl 3:4-13. doi:10.1111/rda.13012
Petersen B, Frenzel A, Lucas-Hahn A, Herrmann D, Hassel P, Klein S, Ziegler M, Hadeler KG, Niemann H (2016) Efficient production of biallelic GGTA1 knockout pigs by cytoplasmic microinjection of CRISPR/Cas9 into zygotes. Xenotransplantation 23(5):338–346. https://doi.org/10.1111/xen.12258
Petters RM, Shuman RM, Johnson BH, Mettus RV (1987) Gene transfer in swine embryos by injection of cells infected with retrovirus vectors. J Exp Zool 242(1):85–88. https://doi.org/10.1002/jez.1402420111
Pfeiffer CA, Meyer AE, Brooks KE, Chen PR, Milano-Foster J, Spate LD, Benne JA, Cecil RF, Samuel MS, Ciernia LA, Spinka CM, Smith MF, Wells KD, Spencer TE, Prather RS, Geisert RD (2020) Ablation of conceptus PTGS2 expression does not alter early conceptus development and establishment of pregnancy in the pigdagger. Biol Reprod 102(2):475–488. https://doi.org/10.1093/biolre/ioz192
Polejaeva IA, Chen SH, Vaught TD, Page RL, Mullins J, Ball S, Dai Y, Boone J, Walker S, Ayares DL, Colman A, Campbell KH (2000) Cloned pigs produced by nuclear transfer from adult somatic cells. Nature 407(6800):86–90. https://doi.org/10.1038/35024082
Prather RS, Sims MM, First NL (1989) Nuclear transplantation in early pig embryos. Biol Reprod 41(3):414–418. https://doi.org/10.1095/biolreprod41.3.414
Prather RS, Rowland RR, Ewen C, Trible B, Kerrigan M, Bawa B, Teson JM, Mao J, Lee K, Samuel MS, Whitworth KM, Murphy CN, Egen T, Green JA (2013) An intact sialoadhesin (Sn/SIGLEC1/CD169) is not required for attachment/internalization of the porcine reproductive and respiratory syndrome virus. J Virol 87(17):9538–9546. https://doi.org/10.1128/JVI.00177-13
Ramlee MK, Yan T, Cheung AMS, Chuah CTH, Li S (2015) High-throughput genotyping of CRISPR/Cas9-mediated mutants using fluorescent PCR-capillary gel electrophoresis. Scientific Rep 5:15587. doi:https://doi.org/10.1038/srep15587., https://www.nature.com/articles/srep15587#supplementary-information
Ramlee MK, Wang J, Cheung AMS, Li S (2017) Using a Fluorescent PCR-capillary Gel Electrophoresis Technique to Genotype CRISPR/Cas9-mediated Knockout Mutants in a High-throughput Format. J Vis Exp 122. https://doi.org/10.3791/55586
Redel BK, Spate LD, Lee K, Mao J, Whitworth KM, Prather RS (2016) Glycine supplementation in vitro enhances porcine preimplantation embryo cell number and decreases apoptosis but does not lead to live births. Mol Reprod Dev 83(3):246–258. https://doi.org/10.1002/mrd.22618
Robertson E, Bradley A, Kuehn M, Evans M (1986) Germ-line transmission of genes introduced into cultured pluripotential cells by retroviral vector. Nature 323(6087):445–448. https://doi.org/10.1038/323445a0
Rocadembosch J, Amador J, Bernaus J, Font J, Fraile LJ (2016) Production parameters and pig production cost: temporal evolution 2010-2014. Porcine Health Manag 2:11. https://doi.org/10.1186/s40813-016-0027-0
Romar R, Canovas S, Matas C, Gadea J, Coy P (2019) Pig in vitro fertilization: Where are we and where do we go? Theriogenology 137:113–121. https://doi.org/10.1016/j.theriogenology.2019.05.045
Sake HJ, Frenzel A, Lucas-Hahn A, Nowak-Imialek M, Hassel P, Hadeler KG, Hermann D, Becker R, Eylers H, Hein R, Baars W, Brinkmann A, Schwinzer R, Niemann H, Petersen B (2019) Possible detrimental effects of beta-2-microglobulin knockout in pigs. Xenotransplantation 26(6):e12525. https://doi.org/10.1111/xen.12525
Sakurai T, Watanabe S, Kamiyoshi A, Sato M, Shindo T (2014) A single blastocyst assay optimized for detecting CRISPR/Cas9 system-induced indel mutations in mice. BMC Biotechnol 14(1):69. https://doi.org/10.1186/1472-6750-14-69
Sato M, Miyoshi K, Nagao Y, Nishi Y, Ohtsuka M, Nakamura S, Sakurai T, Watanabe S (2014) The combinational use of CRISPR/Cas9-based gene editing and targeted toxin technology enables efficient biallelic knockout of the alpha-1,3-galactosyltransferase gene in porcine embryonic fibroblasts. Xenotransplantation 21(3):291–300. https://doi.org/10.1111/xen.12089
Sato M, Kosuke M, Koriyama M, Inada E, Saitoh I, Ohtsuka M, Nakamura S, Sakurai T, Watanabe S, Miyoshi K (2018) Timing of CRISPR/Cas9-related mRNA microinjection after activation as an important factor affecting genome editing efficiency in porcine oocytes. Theriogenology 108:29–38. https://doi.org/10.1016/j.theriogenology.2017.11.030
Schachtschneider KM, Schwind RM, Darfour-Oduro KA, De AK, Rund LA, Singh K, Principe DR, Guzman G, Ray CE, Jr., Ozer H, Gaba RC, Schook LB (2017) A validated, transitional and translational porcine model of hepatocellular carcinoma. Oncotarget 8 (38):63620-63634. https://doi.org/10.18632/oncotarget.18872
Schook LB, Collares TV, Hu W, Liang Y, Rodrigues FM, Rund LA, Schachtschneider KM, Seixas FK, Singh K, Wells KD, Walters EM, Prather RS, Counter CM (2015) A genetic porcine model of cancer. PLoS One 10(7):e0128864. https://doi.org/10.1371/journal.pone.0128864
Schook LB, Rund L, Begnini KR, Remiao MH, Seixas FK, Collares T (2016) Emerging technologies to create inducible and genetically defined porcine cancer models. Front Genet 7:28. https://doi.org/10.3389/fgene.2016.00028
Sheets TP, Park CH, Park KE, Powell A, Donovan DM, Telugu BP (2016) Somatic cell nuclear transfer followed by CRIPSR/Cas9 microinjection results in highly efficient genome editing in cloned pigs. Int J Mol Sci 17(12):2031. https://doi.org/10.3390/ijms17122031
Sheets TP, Park KE, Park CH, Swift SM, Powell A, Donovan DM, Telugu BP (2018) Targeted mutation of NGN3 gene disrupts pancreatic endocrine cell development in pigs. Scientific Rep 8(1):3582. https://doi.org/10.1038/s41598-018-22050-0
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. https://doi.org/10.1038/nmeth.2857
Shi J, Zhou R, Luo L, Mai R, Zeng H, He X, Liu D, Zeng F, Cai G, Ji H, Tang F, Wang Q, Wu Z, Li Z (2015) Influence of embryo handling and transfer method on pig cloning efficiency. Anim Reprod Sci 154:121–127. https://doi.org/10.1016/j.anireprosci.2015.01.006
Shi X, Tang T, Lin Q, Liu H, Qin Y, Liang X, Cong P, Mo D, Liu X, Chen Y, He Z (2020) Efficient generation of bone morphogenetic protein 15-edited Yorkshire pigs using CRISPR/Cas9dagger. Biol Reprod 103(5):1054–1068. https://doi.org/10.1093/biolre/ioaa138
Smedley D, Salimova E, Rosenthal N (2011) Cre recombinase resources for conditional mouse mutagenesis. Methods 53(4):411–416. https://doi.org/10.1016/j.ymeth.2010.12.027
Somfai T, Yoshioka K, Tanihara F, Kaneko H, Noguchi J, Kashiwazaki N, Nagai T, Kikuchi K (2014) Generation of live piglets from cryopreserved oocytes for the first time using a defined system for in vitro embryo production. PLoS One 9(5):e97731. https://doi.org/10.1371/journal.pone.0097731
Song Y, Lai L, Li L, Huang Y, Wang A, Tang X, Pang D, Li Z, Ouyang H (2016) Germ cell- specific expression of Cre recombinase using the VASA promoter in the pig. FEBS open bio 6(1):50–55. https://doi.org/10.1002/2211-5463.12005
Soppe JA, Lebbink RJ (2017) Antiviral goes viral: harnessing CRISPR/Cas9 to combat viruses in humans. Trends Microbiol 25(10):833–850. https://doi.org/10.1016/j.tim.2017.04.005
Sperandio S, Lulli V, Bacci ML, Forni M, Maione B, Spadafora C, Lavitrano M (1996) Sperm mediated gene transfer in bovine and swine species. Anim Biotech 7:59–77
Su X, Chen W, Cai Q, Liang P, Chen Y, Cong P, Huang J (2020) Effective generation of maternal genome point mutated porcine embryos by injection of cytosine base editor into germinal vesicle oocytes. Sci China Life Sci 63(7):996–1005. https://doi.org/10.1007/s11427-019-1611-1
Sun JM, Cui KQ, Li ZP, Lu XR, Xu ZF, Liu QY, Huang B, Shi DS (2017) Suberoylanilide hydroxamic acid, a novel histone deacetylase inhibitor, improves the development and acetylation level of miniature porcine handmade cloning embryos. Reprod Domes Anim 52(5):763–774. https://doi.org/10.1111/rda.12977
Tajima S, Uchikura K, Kurita T, Kikuchi K (2020) Insemination of recipient sows improves the survival to term of vitrified and warmed porcine expanded blastocysts transferred non- surgically. Anim Sci J Nihon chikusan Gakkaiho 91 (1):e13453. https://doi.org/10.1111/asj.13453
Tanihara F, Takemoto T, Kitagawa E, Rao S, Do LT, Onishi A, Yamashita Y, Kosugi C, Suzuki H, Sembon S, Suzuki S, Nakai M, Hashimoto M, Yasue A, Matsuhisa M, Noji S, Fujimura T, Fuchimoto D, Otoi T (2016) Somatic cell reprogramming-free generation of genetically modified pigs. Sci Adv 2(9):e1600803. https://doi.org/10.1126/sciadv.1600803
Tanihara F, Hirata M, Nguyen NT, Le QA, Hirano T, Takemoto T, Nakai M, Fuchimoto DI, Otoi T (2018) Generation of a TP53-modified porcine cancer model by CRISPR/Cas9- mediated gene modification in porcine zygotes via electroporation. PLoS One 13(10):e0206360. https://doi.org/10.1371/journal.pone.0206360
Tanihara F, Hirata M, Nguyen NT, Le QA, Hirano T, Takemoto T, Nakai M, Fuchimoto DI, Otoi T (2019a) Generation of PDX-1 mutant porcine blastocysts by introducing CRISPR/Cas9-system into porcine zygotes via electroporation. Anim Sci J Nihon chikusan Gakkaiho 90(1):55–61. https://doi.org/10.1111/asj.13129
Tanihara F, Hirata M, Nguyen NT, Le QA, Wittayarat M, Fahrudin M, Hirano T, Otoi T (2019b) Generation of CD163-edited pig via electroporation of the CRISPR/Cas9 system into porcine in vitro-fertilized zygotes. Anim Biotechnol:1–8. doi:https://doi.org/10.1080/10495398.2019.1668801
Tanihara F, Hirata M, Nguyen NT, Sawamoto O, Kikuchi T, Doi M, Otoi T (2020a) Efficient generation of GGTA1-deficient pigs by electroporation of the CRISPR/Cas9 system into in vitro-fertilized zygotes. BMC Biotechnol 20(1):40. https://doi.org/10.1186/s12896-020-00638-7
Tanihara F, Hirata M, Thi Nguyen N, Anh Le Q, Hirano T, Otoi T (2020b) Generation of viable PDX1 gene-edited founder pigs as providers of nonmosaics. Mol Reprod Dev 87 (4):471–481. doi:https://doi.org/10.1002/mrd.23335
Tanihara F, Hirata M, Nguyen NT, Sawamoto O, Kikuchi T, Otoi T (2021) One-step generation of multiple gene-edited pigs by electroporation of the CRISPR/Cas9 system into zygotes to reduce xenoantigen biosynthesis. Intl J Mol Sci 22(5):2249
Tao L, Yang M, Wang X, Zhang Z, Wu Z, Tian J, An L, Wang S (2016) Efficient biallelic mutation in porcine parthenotes using a CRISPR-Cas9 system. Biochem Biophys Res Commun 476(4):225–229. https://doi.org/10.1016/j.bbrc.2016.05.100
Taweechaipaisankul A, Kim GA, Jin JX, Lee S, Qasim M, Kim EH, Lee BC (2019) Enhancement of epigenetic reprogramming status of porcine cloned embryos with zebularine, a DNA methyltransferase inhibitor. Mol Reprod Dev 86(8):1013–1022. https://doi.org/10.1002/mrd.23178
Tu Z, Yang W, Yan S, Guo X, Li XJ (2015) CRISPR/Cas9: a powerful genetic engineering tool for establishing large animal models of neurodegenerative diseases. Mol Neurodegener 10(1):35. https://doi.org/10.1186/s13024-015-0031-x
Tu Z, Yang W, Yan S, Yin A, Gao J, Liu X, Zheng Y, Zheng J, Li Z, Yang S, Li S, Guo X, Li XJ (2017) Promoting Cas9 degradation reduces mosaic mutations in non-human primate embryos. Scientific reports 7(1):42081. https://doi.org/10.1038/srep42081
Ulloa Ullo CM, Yoshizawa M, Komoriya E, Mitsui A, Nagai T, Kikuchi K (2008) The blastocyst production rate and incidence of chromosomal abnormalities by developmental stage in in vitro produced porcine embryos. J Reprod Dev 54(1):22–29. https://doi.org/10.1262/jrd.19102
Vajta G, Zhang Y, Machaty Z (2007) Somatic cell nuclear transfer in pigs: recent achievements and future possibilities. Reprod Fertil Dev 19(2):403–423. https://doi.org/10.1071/rd06089
Van Eenennaam AL, Silva FF, Trott JF, Zilberman D (2020) Genetic engineering of livestock: the opportunity cost of regulatory delay. Ann Rev Anim Biosci 9 (1):null. https://doi.org/10.1146/annurev-animal-061220-023052
Vanamee ES, Santagata S, Aggarwal AK (2001) FokI requires two specific DNA sites for cleavage. J Mol Biol 309(1):69–78. https://doi.org/10.1006/jmbi.2001.4635
Wall RJ, Pursel VG, Hammer RE, Brinster RL (1985) Development of porcine ova that were centrifuged to permit visualization of pronuclei and nuclei. Biol Reprod 32(3):645–651. https://doi.org/10.1095/biolreprod32.3.645
Wang K, Ouyang H, Xie Z, Yao C, Guo N, Li M, Jiao H, Pang D (2015a) Efficient generation of myostatin mutations in pigs using the CRISPR/Cas9 system. Scientific Rep 5(1):16623. https://doi.org/10.1038/srep16623
Wang X, Zhou J, Cao C, Huang J, Hai T, Wang Y, Zheng Q, Zhang H, Qin G, Miao X, Wang H, Cao S, Zhou Q, Zhao J (2015b) Efficient CRISPR/Cas9-mediated biallelic gene disruption and site-specific knockin after rapid selection of highly active sgRNAs in pigs. Scientific reports 5:13348. https://doi.org/10.1038/srep13348
Wang Y, Du Y, Shen B, Zhou X, Li J, Liu Y, Wang J, Zhou J, Hu B, Kang N, Gao J, Yu L, Huang X, Wei H (2015c) Efficient generation of gene-modified pigs via injection of zygote with Cas9/sgRNA. Scientific reports 5(1):8256. https://doi.org/10.1038/srep08256
Wang X, Cao C, Huang J, Yao J, Hai T, Zheng Q, Wang X, Zhang H, Qin G, Cheng J, Wang Y, Yuan Z, Zhou Q, Wang H, Zhao J (2016) One-step generation of triple gene-targeted pigs using CRISPR/Cas9 system. Scientific reports 6(1):20620. https://doi.org/10.1038/srep20620
Wang HX, Li M, Lee CM, Chakraborty S, Kim HW, Bao G, Leong KW (2017a) CRISPR/Cas9- Based Genome Editing for Disease Modeling and Therapy: Challenges and Opportunities for Nonviral Delivery. Chem Rev 117(15):9874–9906. https://doi.org/10.1021/acs.chemrev.6b00799
Wang K, Tang X, Xie Z, Zou X, Li M, Yuan H, Guo N, Ouyang H, Jiao H, Pang D (2017b) CRISPR/Cas9-mediated knockout of myostatin in Chinese indigenous Erhualian pigs. Transgenic Res. https://doi.org/10.1007/s11248-017-0044-z
Wang H, Shen L, Chen J, Liu X, Tan T, Hu Y, Bai X, Li Y, Tian K, Li N, Hu X (2019a) Deletion of CD163 Exon 7 Confers Resistance to Highly Pathogenic Porcine Reproductive and Respiratory Viruses on Pigs. Int J Biol Sci 15(9):1993–2005. https://doi.org/10.7150/ijbs.34269
Wang J, Liu M, Zhao L, Li Y, Zhang M, Jin Y, Xiong Q, Liu X, Zhang L, Jiang H, Chen Q, Wang C, You Z, Yang H, Cao C, Dai Y, Li R (2019b) Disabling of nephrogenesis in porcine embryos via CRISPR/Cas9-mediated SIX1 and SIX4 gene targeting. Xenotransplantation 26(3):e12484. https://doi.org/10.1111/xen.12484
Wang H, Li G, Zhong C, Mo J, Sun Y, Shi J, Zhou R, Li Z, Wu Z, Liu D, Zhang X (2020) Generation of Multi-Transgenic Pigs Using PiggyBac Transposons Co-expressing Pectinase, Xylanase, Cellulase, beta-1.3-1.4-Glucanase and Phytase. Front Genet 11 (1521):597841. https://doi.org/10.3389/fgene.2020.597841
Wasmer M (2019) Roads forward for European GMO policy-uncertainties in wake of ECJ judgment have to be mitigated by regulatory reform. Front Bioeng Biotechnol 7 (JUN):132. doi:https://doi.org/10.3389/fbioe.2019.00132
Wells KD, Prather RS (2017) Genome-editing technologies to improve research, reproduction, and production in pigs. Mol Reprod Dev 84(9):1012–1017. https://doi.org/10.1002/mrd.22812
Whitelaw CB, Sang HM (2005) Disease-resistant genetically modified animals. Rev Sci Tech 24(1):275–283
Whitelaw CB, Sheets TP, Lillico SG, Telugu BP (2016) Engineering large animal models of human disease. J Pathol 238(2):247–256. https://doi.org/10.1002/path.4648
Whitworth KM, Prather RS (2017) Gene editing as applied to prevention of reproductive porcine reproductive and respiratory syndrome. Mol Reprod Dev 84(9):926–933. https://doi.org/10.1002/mrd.22811
Whitworth KM, Li R, Spate LD, Wax DM, Rieke A, Whyte JJ, Manandhar G, Sutovsky M, Green JA, Sutovsky P, Prather RS (2009) Method of oocyte activation affects cloning efficiency in pigs. Mol Reprod Dev 76(5):490–500. https://doi.org/10.1002/mrd.20987
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 (2014) Use of the CRISPR/Cas9 system to produce genetically engineered pigs from in vitro-derived oocytes and embryos. Biol Reprod 91(3):78. https://doi.org/10.1095/biolreprod.114.121723
Whitworth KM, Rowland RR, Ewen CL, Trible BR, Kerrigan MA, Cino-Ozuna AG, Samuel MS, Lightner JE, McLaren DG, Mileham AJ, Wells KD, Prather RS (2016) Gene-edited pigs are protected from porcine reproductive and respiratory syndrome virus. Nat Biotechnol 34(1):20–22. https://doi.org/10.1038/nbt.3434
Whitworth KM, Benne JA, Spate LD, Murphy SL, Samuel MS, Murphy CN, Richt JA, Walters E, Prather RS, Wells KD (2017) Zygote injection of CRISPR/Cas9 RNA successfully modifies the target gene without delaying blastocyst development or altering the sex ratio in pigs. Transgenic Res 26(1):97–107. https://doi.org/10.1007/s11248-016-9989-6
Whitworth KM, Cecil R, Benne JA, Redel BK, Spate LD, Samuel MS, Prather RS, Wells KD (2018) Zygote injection of RNA encoding Cre recombinase results in efficient removal of LoxP flanked neomycin cassettes in pigs. Transgenic Res 27(2):167–178. https://doi.org/10.1007/s11248-018-0064-3
Whitworth KM, Rowland RRR, Petrovan V, Sheahan M, Cino-Ozuna AG, Fang Y, Hesse R, Mileham A, Samuel MS, Wells KD, Prather RS (2019) Resistance to coronavirus infection in amino peptidase N-deficient pigs. Transgenic Res 28(1):21–32. https://doi.org/10.1007/s11248-018-0100-3
Whyte JJ, Meyer AE, Spate LD, Benne JA, Cecil R, Samuel MS, Murphy CN, Prather RS, Geisert RD (2018) Inactivation of porcine interleukin-1beta results in failure of rapid conceptus elongation. Proc Natl Acad Sci U S A 115(2):307–312. https://doi.org/10.1073/pnas.1718004115
Wolfe SA, Nekludova L, Pabo CO (2000) DNA recognition by Cys2His2 zinc finger proteins. Annu Rev Biophys Biomol Struct. 29. https://doi.org/10.1146/annurev.biophys.29.1.183
Wu J, Vilarino M, Suzuki K, Okamura D, Bogliotti YS, Park I, Rowe J, McNabb B, Ross PJ, Belmonte JCI (2017) CRISPR-Cas9 mediated one-step disabling of pancreatogenesis in pigs. Scientific reports 7(1):10487. https://doi.org/10.1038/s41598-017-08596-5
Wu H, Liu Q, Shi H, Xie J, Zhang Q, Ouyang Z, Li N, Yang Y, Liu Z, Zhao Y, Lai C, Ruan D, Peng J, Ge W, Chen F, Fan N, Jin Q, Liang Y, Lan T, Yang X, Wang X, Lei Z, Doevendans PA, Sluijter JPG, Wang K, Li X, Lai L (2018) Engineering CRISPR/Cpf1 with tRNA promotes genome editing capability in mammalian systems. Cell Mol Life Sci 75(19):3593–3607. https://doi.org/10.1007/s00018-018-2810-3
Xie Z, Pang D, Wang K, Li M, Guo N, Yuan H, Li J, Zou X, Jiao H, Ouyang H, Li Z, Tang X (2017) Optimization of a CRISPR/Cas9-mediated Knock-in strategy at the Porcine Rosa26 locus in porcine foetal fibroblasts. Scientific reports 7(1):3036. https://doi.org/10.1038/s41598-017-02785-y
Xie Z, Pang D, Yuan H, Jiao H, Lu C, Wang K, Yang Q, Li M, Chen X, Yu T, Chen X, Dai Z, Peng Y, Tang X, Li Z, Wang T, Guo H, Li L, Tu C, Lai L, Ouyang H (2018) Genetically modified pigs are protected from classical swine fever virus. PLoS pathogens 14(12):e1007193. https://doi.org/10.1371/journal.ppat.1007193
Xie J, Ge W, Li N, Liu Q, Chen F, Yang X, Huang X, Ouyang Z, Zhang Q, Zhao Y, Liu Z, Gou S, Wu H, Lai C, Fan N, Jin Q, Shi H, Liang Y, Lan T, Quan L, Li X, Wang K, Lai L (2019) Efficient base editing for multiple genes and loci in pigs using base editors. Nat Commun 10(1):2852. https://doi.org/10.1038/s41467-019-10421-8
Xie F, Zhou X, Lin T, Wang L, Liu C, Luo X, Luo L, Chen H, Guo K, Wei H, Wang Y (2020a) Production of gene-edited pigs harboring orthologous human mutations via double cutting by CRISPR/Cas9 with long single-stranded DNAs as homology-directed repair templates by zygote injection. Transgenic Res 29(5-6):587–598. https://doi.org/10.1007/s11248-020-00218-7
Xie Z, Jiao H, Xiao H, Jiang Y, Liu Z, Qi C, Zhao D, Jiao S, Yu T, Tang X, Pang D, Ouyang H (2020b) Generation of pRSAD2 gene knock-in pig via CRISPR/Cas9 technology. Antiviral Res 174:104696. https://doi.org/10.1016/j.antiviral.2019.104696
Xu K, Zhou Y, Mu Y, Liu Z, Hou S, Xiong Y, Fang L, Ge C, Wei Y, Zhang X, Xu C, Che J, Fan Z, Xiang G, Guo J, Shang H, Li H, Xiao S, Li J, Li K (2020) CD163 and pAPN double- knockout pigs are resistant to PRRSV and TGEV and exhibit decreased susceptibility to PDCoV while maintaining normal production performance. eLife 9:e57132. doi:https://doi.org/10.7554/eLife.57132
Yamashita S, Kogasaka Y, Hiradate Y, Tanemura K, Sendai Y (2020) Suppression of mosaic mutation by co-delivery of CRISPR associated protein 9 and three-prime repair exonuclease 2 into porcine zygotes via electroporation. J Reprod Dev 66(1):41–48. https://doi.org/10.1262/jrd.2019-088
Yang H, Wu Z (2018) Genome Editing of Pigs for Agriculture and Biomedicine. Front Genet 9:360. https://doi.org/10.3389/fgene.2018.00360
Yang L, Guell M, Niu D, George H, Lesha E, Grishin D, Aach J, Shrock E, Xu W, Poci J, Cortazio R, Wilkinson RA, Fishman JA, Church G (2015) Genome-wide inactivation of porcine endogenous retroviruses (PERVs). Science 350(6264):1101–1104. https://doi.org/10.1126/science.aad1191
Yang H, Zhang J, Zhang X, Shi J, Pan Y, Zhou R, Li G, Li Z, Cai G, Wu Z (2018) CD163 knockout pigs are fully resistant to highly pathogenic porcine reproductive and respiratory syndrome virus. Antiviral Res 151:63–70. https://doi.org/10.1016/j.antiviral.2018.01.004
Yao J, Huang J, Zhao J (2016) Genome editing revolutionize the creation of genetically modified pigs for modeling human diseases. Hum Genet 135(9):1093–1105. https://doi.org/10.1007/s00439-016-1710-6
Yao J, Zeng H, Zhang M, Wei Q, Wang Y, Yang H, Lu Y, Li R, Xiong Q, Zhang L, Chen Z, Xing G, Cao X, Dai Y (2019) OSBPL2-disrupted pigs recapitulate dual features of human hearing loss and hypercholesterolaemia. J Genetics Genom Yi chuan xue bao 46(8):379–387. https://doi.org/10.1016/j.jgg.2019.06.006
Yin Y, Hao H, Xu X, Shen L, Wu W, Zhang J, Li Q (2019) Generation of an MC3R knock-out pig by CRSPR/Cas9 combined with somatic cell nuclear transfer (SCNT) technology. Lipids in health and disease 18(1):122. https://doi.org/10.1186/s12944-019-1073-9
Yoshioka K, Suzuki C, Tanaka A, Anas IM, Iwamura S (2002) Birth of piglets derived from porcine zygotes cultured in a chemically defined medium. Biol Reprod 66(1):112–119. https://doi.org/10.1095/biolreprod66.1.112
Yoshioka K, Suzuki C, Itoh S, Kikuchi K, Iwamura S, Rodriguez-Martinez H (2003) Production of piglets derived from in vitro-produced blastocysts fertilized and cultured in chemically defined media: effects of theophylline, adenosine, and cysteine during in vitro fertilization. Biol Reprod 69(6):2092–2099. https://doi.org/10.1095/biolreprod.103.020081
Yoshioka K, Noguchi M, Suzuki C (2012) Production of piglets from in vitro-produced embryos following non-surgical transfer. Anim Reprod Sci 131(1-2):23–29. https://doi.org/10.1016/j.anireprosci.2012.01.018
Youngs CR (2001) Factors influencing the success of embryo transfer in the pig. Theriogenology 56(8):1311–1320. https://doi.org/10.1016/s0093-691x(01)00632-x
Yu HH, Zhao H, Qing YB, Pan WR, Jia BY, Zhao HY, Huang XX, Wei HJ (2016) Porcine Zygote Injection with Cas9/sgRNA Results in DMD-Modified Pig with Muscle Dystrophy. Int J Mol Sci 17(10). https://doi.org/10.3390/ijms17101668
Yuan Y, Spate LD, Redel BK, Tian Y, Zhou J, Prather RS, Roberts RM (2017) Quadrupling efficiency in production of genetically modified pigs through improved oocyte maturation. Proc Natl Acad Sci U S A 114(29):E5796–e5804. https://doi.org/10.1073/pnas.1703998114
Yuan H, Yu T, Wang L, Yang L, Zhang Y, Liu H, Li M, Tang X, Liu Z, Li Z, Lu C, Chen X, Pang D, Ouyang H (2020) Efficient base editing by RNA-guided cytidine base editors (CBEs) in pigs. Cell Mol Life Sci 77(4):719–733. https://doi.org/10.1007/s00018-019-03205-2
Yuk IH, Zhang JD, Ebeling M, Berrera M, Gomez N, Werz S, Meiringer C, Shao Z, Swanberg JC, Lee KH, Luo J, Szperalski B (2014) Effects of copper on CHO cells: insights from gene expression analyses. Biotechnol Prog 30(2):429–442. https://doi.org/10.1002/btpr.1868
Zettler S, Renner S, Kemter E, Hinrichs A, Klymiuk N, Backman M, Riedel EO, Mueller C, Streckel E, Braun-Reichhart C, Martins AS, Kurome M, Kessler B, Zakhartchenko V, Flenkenthaler F, Arnold GJ, Frohlich T, Blum H, Blutke A, Wanke R, Wolf E (2020) A decade of experience with genetically tailored pig models for diabetes and metabolic research. Anim Reprod 17(3):e20200064. https://doi.org/10.1590/1984-3143-AR2020-0064
Zhai Y, Li W, Zhang Z, Cao Y, Wang Z, Zhang S, Li Z (2018) Epigenetic states of donor cells significantly affect the development of somatic cell nuclear transfer (SCNT) embryos in pigs. Mol Reprod Dev 85(1):26–37. https://doi.org/10.1002/mrd.22935
Zhang R, Wang Y, Chen L, Wang R, Li C, Li X, Fang B, Ren X, Ruan M, Liu J, Xiong Q, Zhang L, Jin Y, Zhang M, Liu X, Li L, Chen Q, Pan D, Li R, Cooper DKC, Yang H, Dai Y (2018a) Reducing immunoreactivity of porcine bioprosthetic heart valves by genetically- deleting three major glycan antigens, GGTA1/beta4GalNT2/CMAH. Acta Biomater 72:196–205. https://doi.org/10.1016/j.actbio.2018.03.055
Zhang X, Li Z, Yang H, Liu D, Cai G, Li G, Mo J, Wang D, Zhong C, Wang H, Sun Y, Shi J, Zheng E, Meng F, Zhang M, He X, Zhou R, Zhang J, Huang M, Zhang R, Li N, Fan M, Yang J, Wu Z (2018b) Novel transgenic pigs with enhanced growth and reduced environmental impact. eLife:7. https://doi.org/10.7554/eLife.34286
Zhang B, Wang C, Zhang Y, Jiang Y, Qin Y, Pang D, Zhang G, Liu H, Xie Z, Yuan H, Ouyang H, Wang J, Tang X (2020) A CRISPR-engineered swine model of COL2A1 deficiency recapitulates altered early skeletal developmental defects in humans. Bone 137:115450. https://doi.org/10.1016/j.bone.2020.115450
Zhao J, Ross JW, Hao Y, Spate LD, Walters EM, Samuel MS, Rieke A, Murphy CN, Prather RS (2009) Significant improvement in cloning efficiency of an inbred miniature pig by histone deacetylase inhibitor treatment after somatic cell nuclear transfer. Biol Reprod 81(3):525–530. https://doi.org/10.1095/biolreprod.109.077016
Zheng Q, Lin J, Huang J, Zhang H, Zhang R, Zhang X, Cao C, Hambly C, Qin G, Yao J, Song R, Jia Q, Wang X, Li Y, Zhang N, Piao Z, Ye R, Speakman JR, Wang H, Zhou Q, Wang Y, Jin W, Zhao J (2017) Reconstitution of UCP1 using CRISPR/Cas9 in the white adipose tissue of pigs decreases fat deposition and improves thermogenic capacity. Proc Natl Acad Sci U S A 114(45):E9474–E9482. https://doi.org/10.1073/pnas.1707853114
Zhou X, Xin J, Fan N, Zou Q, Huang J, Ouyang Z, Zhao Y, Zhao B, Liu Z, Lai S, Yi X, Guo L, Esteban MA, Zeng Y, Yang H, Lai L (2015) Generation of CRISPR/Cas9-mediated gene- targeted pigs via somatic cell nuclear transfer. Cell Mol Life Sci 72(6):1175–1184. https://doi.org/10.1007/s00018-014-1744-7
Zhou X, Wang L, Du Y, Xie F, Li L, Liu Y, Liu C, Wang S, Zhang S, Huang X, Wang Y, Wei H (2016) Efficient Generation of Gene-Modified Pigs Harboring Precise Orthologous Human Mutation via CRISPR/Cas9-Induced Homology-Directed Repair in Zygotes. Hum Mutat 37(1):110–118. https://doi.org/10.1002/humu.22913
Zhu XX, Zhong YZ, Ge YW, Lu KH, Lu SS (2018) CRISPR/Cas9-mediated generation of Guangxi Bama minipigs harboring three mutations in alpha-synuclein causing Parkinson’s disease. Scientific Rep 8(1):12420. https://doi.org/10.1038/s41598-018-30436-3
Zhu X, Wei Y, Zhan Q, Yan A, Feng J, Liu L, Tang D (2020a) CRISPR/Cas9-Mediated Biallelic Knockout of IRX3 Reduces the Production and Survival of Somatic Cell-Cloned Bama Minipigs. Animals (Basel) 10(3):501–501. https://doi.org/10.3390/ani10030501
Zhu XX, Zhan QM, Wei YY, Yan AF, Feng J, Liu L, Lu SS, Tang DS (2020b) CRISPR/Cas9- mediated MSTN disruption accelerates the growth of Chinese Bama pigs. Reprod Domes Anim 55(10):1314–1327. https://doi.org/10.1111/rda.13775
Zou Y, Li Z, Zou Y, Hao H, Li N, Li Q (2018) An FBXO40 knockout generated by CRISPR/Cas9 causes muscle hypertrophy in pigs without detectable pathological effects. Biochem Biophys Res Commun 498(4):940–945. https://doi.org/10.1016/j.bbrc.2018.03.085
Zou X, Ouyang H, Yu T, Chen X, Pang D, Tang X, Chen C (2019) Preparation of a new type 2 diabetic miniature pig model via the CRISPR/Cas9 system. Cell Death Dis 10(11):823. https://doi.org/10.1038/s41419-019-2056-5
Zuo E, Cai YJ, Li K, Wei Y, Wang BA, Sun Y, Liu Z, Liu J, Hu X, Wei W, Huo X, Shi L, Tang C, Liang D, Wang Y, Nie YH, Zhang CC, Yao X, Wang X, Zhou C, Ying W, Wang Q, Chen RC, Shen Q, Xu GL, Li J, Sun Q, Xiong ZQ, Yang H (2017) One-step generation of complete gene knockout mice and monkeys by CRISPR/Cas9-mediated gene editing with multiple sgRNAs. Cell Res 27(7):933–945. https://doi.org/10.1038/cr.2017.81
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This work was supported by MINECO-FEDER (AGL 2015-66341-R), Fundación Séneca 20040/GERM/16 and 21105/PDC/19; and FPU fellowship to SNS (FPU16/04480) from Spanish Ministry of Education, Culture and Sport.
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Navarro-Serna, S., Piñeiro-Silva, C., Romar, R., Parrington, J., Gadea, J. (2022). Generation of Gene Edited Pigs. In: Yata, V.K., Mohanty, A.K., Lichtfouse, E. (eds) Sustainable Agriculture Reviews 57. Sustainable Agriculture Reviews, vol 57. Springer, Cham. https://doi.org/10.1007/978-3-031-07496-7_3
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