Evidence that Genome Editing is Preferable to Transgenesis for Enhancing Animal Traits

Jinhai Wang; Shinichi Nakagawa; Jiaqi Wang; Robert Stewart; Alexandra Florea; Rex A. Dunham; Fei Ling; Gaoxue Wang; Lily Liu; Diego Robledo

doi:10.1016/j.eng.2025.11.032

Engineering ›› :202511032 DOI: 10.1016/j.eng.2025.11.032

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Evidence that Genome Editing is Preferable to Transgenesis for Enhancing Animal Traits

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Abstract

Production traits such as growth, disease resistance, and fatty acid content in engineered animals are anticipated to be enhanced via transgenesis (TG) or genome editing (GE). It is, however, unclear whether this expectation is upheld when making global comparisons across taxa. In this study, we performed a meta-analysis of 154 research papers covering 72 species and 55 genes, with the aim of quantifying and comparing the effects of TG and GE on animal production traits through overexpressing or disrupting key genes. Although TG is more commonly used for trait enhancement, GE has more pronounced and widespread effects, particularly on growth and disease resistance traits. This is reflected in larger effect sizes and broader impacts across trait responses. Yet, we observe differences in patterns of trait enhancement that are specific to taxon and parameter. For instance, TG reduces pathogen load in chickens and cattle, but not in pigs; conversely, GE lowers virus RNA levels in pigs, but is less successful in chickens and cattle. In contrast, both TG and GE significantly increase growth rates in ray-finned fish. It is notable that, although transgenes or edited genes remain highly expressed or repressed in Filial 1 (F₁) offspring, the magnitude of trait improvement is diminished compared to the founder generations. This study provides evidence-based insights to assist researchers in refining their methods and directing future investigations into trait enhancement in genetically engineered animals, while also informing policymaking.

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Genetic engineering / Trait enhancement / Livestock / Meta-analysis

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Jinhai Wang, Shinichi Nakagawa, Jiaqi Wang, Robert Stewart, Alexandra Florea, Rex A. Dunham, Fei Ling, Gaoxue Wang, Lily Liu, Diego Robledo. Evidence that Genome Editing is Preferable to Transgenesis for Enhancing Animal Traits. Engineering 202511032 DOI:10.1016/j.eng.2025.11.032

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References

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[1]	Wright AV, Nuñez JK, Doudna JA. Biology and applications of CRISPR systems: harnessing nature’s toolbox for genome engineering. Cell 2016; 164(1-2):29-44.

[2]	Joung JK, Sander JD. TALENs: a widely applicable technology for targeted genome editing. Nat Rev Mol Cell Biol 2013; 14(1):49-55.

[3]	Carroll D. Genome engineering with zinc-finger nucleases. Genetics 2011; 188(4):773-82.

[4]	Coogan M, Alston V, Su B, Khalil K, Elaswad A, Khan M, et al. CRISPR/Cas-9 induced knockout of myostatin gene improves growth and disease resistance in channel catfish (Ictalurus punctatus). Aquaculture 2022; 557:738290.

[5]	Zhou S, Kalds P, Luo Q, Sun K, Zhao X, Gao Y, et al. Optimized Cas9: sgRNA delivery efficiently generates biallelic MSTN knockout sheep without affecting meat quality. BMC Genomics 2022; 23(1):348.

[6]	Dunham RA, Warr GW, Nichols A, Duncan PL, Argue B, Middleton D, et al. Enhanced bacterial disease resistance of transgenic channel catfish Ictalurus punctatus possessing cecropin genes. Mar Biotechnol 2002; 4(3):338-44.

[7]	Clark J, Whitelaw B. A future for transgenic livestock. Nat Rev Genet 2003; 4(10):825-33.

[8]	Wu H, Wang Y, Zhang Y, Yang M, Lv J, Liu J, et al. TALE nickase-mediated SP110 knockin endows cattle with increased resistance to tuberculosis. Proc Natl Acad Sci USA 2015; 112(13):E1530-9.

[9]	Saeki K, Matsumoto K, Kinoshita M, Suzuki I, Tasaka Y, Kano K, et al. Functional expression of a D₁₂ fatty acid desaturase gene from spinach in transgenic pigs. Proc Natl Acad Sci USA 2004; 101(17):6361-6.

[10]	Zhang X, Pang S, Liu C, Wang H, Ye D, Zhu Z, et al. A novel dietary source of EPA and DHA: metabolic engineering of an important freshwater species—common carp by fat1-transgenesis. Mar Biotechnol 2019; 21(2):171-85.

[11]	Coogan M, Xing D, Su B, Alston V, Johnson A, Khan M, et al. CRISPR/Cas9-mediated knock-in of masu salmon (Oncorhyncus masou) elongase gene in the melanocortin-4 (mc4r) coding region of channel catfish (Ictalurus punctatus) genome. Transgenic Res 2023; 32(4):251-64.

[12]	Lin J, Jin M, Yang D, Li Z, Zhang Y, Xiao Q, et al. Adenine base editing-mediated exon skipping restores dystrophin in humanized Duchenne mouse model. Nat Commun 2024; 15(1):5927.

[13]	Hatanaka F, Suzuki K, Shojima K, Yu J, Takahashi Y, Sakamoto A, et al. Therapeutic strategy for spinal muscular atrophy by combining gene supplementation and genome editing. Nat Commun 2024; 15(1):6191.

[14]	Ciccarelli M, Giassetti MI, Miao D, Oatley MJ, Robbins C, Lopez-Biladeau B, et al. Donor-derived spermatogenesis following stem cell transplantation in sterile NANOS 2 knockout males. Proc Natl Acad Sci USA 2020; 117(39):24195-204.

[15]	Theissinger K, Fernandes C, Formenti G, Bista I, Berg PR, Bleidorn C, et al. How genomics can help biodiversity conservation. Trends Genet 2023; 39(7):545-59.

[16]	Clark AJ, Ali S, Archibald AL, Bessos H, Brown P, Harris S, et al. The molecular manipulation of milk composition. Genome 1989; 31(2):950-5.

[17]	Shepelev MV, Kalinichenko SV, Deykin AV, Korobko IV. Production of recombinant proteins in the milk of transgenic animals: current state and prospects. Acta Nat 2018; 10(3):40-7.

[18]	Vize PD, Michalska AE, Ashman R, Lloyd B, Stone BE, Quinn P, et al. Introduction of a porcine growth hormone fusion gene into transgenic pigs promotes growth. J Cell Sci 1988; 90(2):295-300.

[19]	Pursel VG, Mitchell AD, Bee G, Elsasser TH, McMurtry JP, Wall RJ, et al. Growth and tissue accretion rates of swine expressing an insulin-like growth factor I transgene. Anim Biotechnol 2004; 15(1):33-45.

[20]	Adams NR, Briegel JR, Ward KA. The impact of a transgene for ovine growth hormone on the performance of two breeds of sheep. J Anim Sci 2002; 80(9):2325-33.

[21]	Adams NR, Briegel JR, Pethick DW, Cake MA. Carcass and meat characteristics of sheep with an additional growth hormone gene. Aust J Agric Res 2006; 57(12):1321-5.

[22]	Du SJ, Gong Z, Fletcher GL, Shears MA, King MJ, Idler DR, et al. Growth enhancement in transgenic Atlantic salmon by the use of an “all fish” chimeric growth hormone gene construct. Nat Biotechnol 1992; 10(2):176-81.

[23]	Devlin RH, Yesaki TY, Biagi CA, Donaldson EM, Swanson P, Chan W. Extraordinary salmon growth. Nature 1994; 371(6494):209-10.

[24]	Zhang P, Hayat M, Joyce C, Gonzalez-Villaseñor LI, Lin CM, Dunham RA, et al. Gene transfer, expression and inheritance of PRSV-rainbow trout-GH cDNA in the common carp, Cyprinus carpio (Linnaeus). Mol Reprod Dev 1990; 25(1):3-13.

[25]	Rahman MA, Mak R, Ayad H, Smith A, Maclean N. Expression of a novel piscine growth hormone gene results in growth enhancement in transgenic tilapia (Oreochromis niloticus). Transgenic Res 1998; 7(5):357-70.

[26]	Dunham RA, Eash J, Askins J, Townes TM. Transfer of the metallothionein-human growth hormone fusion gene into channel catfish. Trans Am Fish Soc 1987; 116(1):87-91.

[27]	Kues WA, Niemann H. Advances in farm animal transgenesis. Prev Vet Med 2011; 102(2):146-56.

[28]	Wang J, Cheng Y, Su B, Dunham RA. Genome manipulation advances in selected aquaculture organisms. Rev Aquacult 2025; 17(1):e12988.

[29]	Ledford H. Salmon approval heralds rethink of transgenic animals. Nature 2015; 527(7579):417-8.

[30]	Waltz E. First genetically engineered salmon sold in Canada. Nature 2017; 548(7666):148.

[31]

US Food and Drug Administration. FDA approves first-of-its-kind intentional genomic alteration in line of domestic pigs for both human food, potential therapeutic uses [Internet]. Chicago: Cision US Inc.; 2020 Dec 14 [cited 2025 Nov 10]. Available from: https://www.prnewswire.com/news-releases/fda-approves-first-of-its-kind-intentional-genomic-alteration-in-line-of-domestic-pigs-for-both-human-food-potential-therapeutic-uses-301192244.html.

[32]	Van Eenennaam AL, Wells KD, Murray JD. Proposed US regulation of gene-edited food animals is not fit for purpose. npj SciFood 2019; 3:3.

[33]	British Public Service Broadcaster (BBC). The great gene editing debate: can it be safe and ethical? London: BBC News; 2024 Sep 11 [cited 2025 Nov 10]. Available from: https://www.bbc.com/news/articles/c74j2lz88pwo.

[34]	Japan embraces CRISPR-edited fish. Nat Biotechnol 2022; 40(1):10.

[35]	Bee G, Pursel VG, Mitchell AD, Maruyama K, Wells KD, Solomon MB, et al. Carcass composition and skeletal muscle morphology of swine expressing an insulin-like growth factor I transgene. Arch Tierzucht 2007; 50(5):501-19.

[36]	Qian L, Tang M, Yang J, Wang Q, Cai C, Jiang S, et al. Targeted mutations in myostatin by zinc-finger nucleases result in double-muscled phenotype in Meishan pigs. Sci Rep 2015; 5(1):14435.

[37]	Bi Y, Hua Z, Liu X, Hua W, Ren H, Xiao H, et al. Isozygous and selectable marker free MSTN knockout cloned pigs generated by the combined use of CRISPR/Cas9 and Cre/LoxP. Sci Rep 2016; 6(1):31729.

[38]	Wu Y, Wu T, Yang L, Su Y, Zhao C, Li L, et al. Generation of fast growth Nile tilapia (Oreochromis niloticus) by myostatin gene mutation. Aquaculture 2023; 562:738762.

[39]	Kang J, Kim S, Zhu H, Jin L, Guo Q, Li X, et al. Generation of cloned adult muscular pigs with myostatin gene mutation by genetic engineering. RSC Adv 2017; 7(21):12541-9.

[40]	Kim G, Lee JH, Song S, Kim SW, Han JS, Shin SP, et al. Generation of myostatin-knockout chickens mediated by D10A-Cas9 nickase. FASEB J 2020; 34(4):5688-96.

[41]	Khalil K, Elayat M, Khalifa E, Daghash S, Elaswad A, Miller M, et al. Generation of myostatin gene edited channel catfish (Ictalurus punctatus) via zygote injection of CRISPR/Cas9 system. Sci Rep 2017; 7(1):7301.

[42]	Shahi N, Mallik SK, Sarma D. Muscle growth in targeted knockout common carp (Cyprinus carpio) mstn gene with low off-target effects. Aquaculture 2022; 547:737423.

[43]	Kim J, Kim J, Cho JY, Shin Y, Son H, Sathiyamoorthy S, et al. Association between muscle growth and transcription of a mutant MSTN gene in olive flounder (Paralichthys olivaceus). Mar Biotechnol 2024; 26(3):599-608.

[44]	Pridgeon JW, Klesius PH, Dominowski PJ, Yancey RJ, Kievit MS. Chicken-type lysozyme in channel catfish: expression analysis, lysozyme activity, and efficacy as immunostimulant against Aeromonas hydrophila infection. Fish Shellfish Immunol 2013; 35(3):680-8.

[45]	Mao W, Wang Y, Wang W, Wu B, Feng J, Zhun Z. Enhanced resistance to Aeromonas hydrophila infection and enhanced phagocytic activities in human lactoferrin-transgenic grass carp (Ctenopharyngodon idellus). Aquaculture 2004; 242(1-4):93-103.

[46]	Whitworth KM, Rowland R, Ewen C, Trible BR, Kerrigan MA, Cino-Ozuna AG, et al. Gene-edited pigs are protected from porcine reproductive and respiratory syndrome virus. Nat Biotechnol 2016; 34(1):20-2.

[47]

Wells KD, Bardot R, Whitworth KM, Trible BR, Fang Y, Mileham A, et al. Replacement of porcine CD163 scavenger receptor cysteine-rich domain 5 with a CD163-like homolog confers resistance of pigs to genotype 1 but not genotype 2 porcine reproductive and respiratory syndrome virus. J Virol 2017; 91(2):e01521-e1616.

[48]

Burkard C, Lillico SG, Reid E, Jackson B, Mileham AJ, Ait-Ali T, et al. 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 Pathog 2017; 13(2):e1006206.

[49]	Salgado B, Rivas RB, Pinto D, Sonstegard TS, Carlson DF, Martins K, et al. Genetically modified pigs lacking CD163 PSTII-domain-coding exon 13 are completely resistant to PRRSV infection. Antiviral Res 2024; 221:105793.

[50]	Popescu LN, Gaudreault NN, Whitworth KM, Murgia MV, Nietfeld JC, Mileham A, et al.Genetically edited pigs lacking CD163 show no resistance following infection with the African swine fever virus isolate, Georgia 2007/1. Virology 2017; 501:102-6.

[51]	Wu X, Ouyang H, Duan B, Pang D, Zhang L, Yuan T, et al. Production of cloned transgenic cow expressing omega-3 fatty acids. Transgenic Res 2012; 21(3):537-43.

[52]	Liu X, Pang D, Yuan T, Li Z, Li Z, Zhang M, et al. N-3 polyunsaturated fatty acids attenuates triglyceride and inflammatory factors level in hfat-1 transgenic pigs. Lipids Health Dis 2016; 15(1):89.

[53]	Lai L, Kang JX, Li R, Wang J, Witt WT, Yong HY, et al. Generation of cloned transgenic pigs rich in omega-3 fatty acids. Nat Biotechnol 2006; 24(4):435-6.

[54]	Li M, Ouyang H, Yuan H, Li J, Xie Z, Wang K, et al. Site-specific fat-1 knock-in enables significant decrease of n-6 PUFAs/n-3 PUFAs ratio in pigs. G3: Genes Genomes Genet 2018; 8(5):1747-54.

[55]	Xing D, Su B, Li S, Bangs M, Creamer D, Coogan M, et al. CRISPR/Cas9-mediated transgenesis of the masu salmon (Oncorhynchus masou) elovl 2 gene improves n-3 fatty acid content in channel catfish (Ictalurus punctatus). Mar Biotechnol 2022; 24(3):513-23.

[56]	O’Dea RE, Lagisz M, Jennions MD, Koricheva J, Noble DW, Parker TH, et al. Preferred reporting items for systematic reviews and meta-analyses in ecology and evolutionary biology: a PRISMA extension. Biol Rev Camb Philos Soc 2021; 96(5):1695-722.

[57]	Tait-Burkard C, Doeschl-Wilson A, McGrew MJ, Archibald AL, Sang HM, Houston R, et al. Livestock 2.0—genome editing for fitter, healthier, and more productive farmed animals. Genome Biol 2018; 19(1):204.

[58]	Telugu BP, Park KE, Park CH. Genome editing and genetic engineering in livestock for advancing agricultural and biomedical applications. Mamm Genome 2017; 28(7-8):338-47.

[59]	Bishop TF, van Eenennaam AL. Genome editing approaches to augment livestock breeding programs. J Exp Biol 2020; 223(1 Suppl 1):jeb207159.

[60]	Park JS, Lee KY, Han JY. Precise genome editing in poultry and its application to industries. Genes 2020; 11(10):1182.

[61]	Khwatenge CN, Nahashon SN. Recent advances in the application of CRISPR/Cas9 gene editing system in poultry species. Front Genet 2021; 12:627714.

[62]	Söllner JH, Mettenleiter TC, Petersen B. Genome editing strategies to protect livestock from viral infections. Viruses 2021; 13(10):1996.

[63]	Gao F, Hou N, Du X, Wang Y, Zhao J, Wu S. Molecular breeding of farm animals through gene editing. Natl Sci Open 2023; 2(5):20220066.

[64]	Wang J, Cheng Y. Enhancing aquaculture disease resistance: antimicrobial peptides and gene editing. Rev Aquacult 2024; 16(1):433-51.

[65]	Jennions MD, Lortie CJ, Rosenberg MS, Rothstein HR. In:Handbook of meta-analysis in ecology and evolution. Princeton: Princeton University Press; 2013. p. 207-36.

[66]	Hedges LV, Olkin I. Random effects models for effect sizes. In: Hedges LV, Olkin I, editors. Statistical methods for meta-analysis. Amsterdam: Academic Press; 1985. p. 189-203.

[67]	Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Softw 2010; 36(3):1-48.

[68]	Cohen J. The concepts of power analysis. In: Cohen J, editor. Statistical power analysis for the behavioral sciences. Amsterdam: Academic Press; 1977. p. 1-17.

[69]	Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21(11):1539-58.

[70]	Nakagawa S, Lagisz M, O’Dea RE, Pottier P, Rutkowska J, Senior AM, et al. OrchaRd 2.0: an R package for visualising meta-analyses with orchard plots. Methods Ecol Evol 2023; 14(8):2003-10.

[71]	Park TS, Park J, Lee JH, Park JW, Park BC. Disruption of G0/G1 switch gene 2 (G0S2) reduced abdominal fat deposition and altered fatty acid composition in chicken. FASEB J 2019; 33(1):1188-98.

[72]	Nakagawa S, Lagisz M, Jennions MD, Koricheva J, Noble DWA, Parker TH, et al. Methods for testing publication bias in ecological and evolutionary meta-analyses. Methods Ecol Evol 2022; 13(1):4-21.

[73]	Duval S, Tweedie R. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 2000; 56(2):455-63.

[74]	Viechtbauer W, Cheung MWL. Outlier and influence diagnostics for meta-analysis. Res Synth Methods 2010; 1(2):112-25.

[75]	Kemper KE, Visscher PM, Goddard ME. Genetic architecture of body size in mammals. Genome Biol 2012; 13(4):244.

[76]	Ellegren H, Galtier N. Determinants of genetic diversity. Nat Rev Genet 2016; 17(7):422-33.

[77]	Devlin RH, Leggatt RA, Benfey TJ. Genetic modification of growth in fish species used in aquaculture: phenotypic and physiological responses. Fish Physiol 2020; 38:237-72.

[78]	Trancoso I, Morimoto R, Boehm T. Co-evolution of mutagenic genome editors and vertebrate adaptive immunity. Curr Opin Immunol 2020; 65:32-41.

[79]	Boehm T. Understanding vertebrate immunity through comparative immunology. Nat Rev Immunol 2025; 25(2):141-52.

[80]	Mitchell SJ, Scheibye-Knudsen M, Longo DL, de Cabo R. Animal models of aging research: implications for human aging and age-related diseases. Annu Rev Anim Biosci 2015; 3(1):283-303.

[81]	Tang S, Ou J, Sun D, Zhang Y, Xu G, Zhang Y. A novel 62-bp indel mutation in the promoter region of transforming growth factor-beta 2 (TGFB2) gene is associated with body weight in chickens. Anim Genet 2011; 42(1):108-12.

[82]	Kishimoto K, Washio Y, Yoshiura Y, Toyoda A, Ueno T, Fukuyama H, et al. Production of a breed of red sea bream Pagrus major with an increase of skeletal muscle mass and reduced body length by genome editing with CRISPR/Cas9. Aquaculture 2018; 495:415-27.

[83]	Liu Z, Zhou T, Gao D. Genetic and epigenetic regulation of growth, reproduction, disease resistance and stress responses in aquaculture. Front Genet 2022; 13:994471.

[84]	Houston RD, Bean TP, Macqueen DJ, Gundappa MK, Jin YH, Jenkins TL, et al. Harnessing genomics to fast-track genetic improvement in aquaculture. Nat Rev Genet 2020; 21(7):389-409.

[85]	Lee H, Yoon DE, Kim K. Genome editing methods in animal models. Anim Cells Syst 2020; 24(1):8-16.

[86]	Pavelin J, Jin YH, Gratacap RL, Taggart JB, Hamilton A, Verner-Jeffreys DW, et al. The nedd-8 activating enzyme gene underlies genetic resistance to infectious pancreatic necrosis virus in Atlantic salmon. Genomics 2021; 113(6):3842-50.

[87]	Wang J, Su B, Dunham RA. Genome-wide identification of catfish antimicrobial peptides: a new perspective to enhance fish disease resistance. Rev Aquacult 2022; 14(4):2002-22.