基因编辑猪的应用进展

doi:10.16174/j.issn.1673-4645.2025.02.004

摘要/Abstract

摘要： 基因编辑技术能够精确靶向修饰生物体基因组特定位点，在农业生物的遗传改良和生物医学研究领域得到了广泛应用，特别是在猪的基因编辑技术和新材料创制工作中取得了显著进展。本文旨在讨论基因编辑猪的技术和应用进展，探讨其在农业生产、生物医学研究和伦理监管方面的现状与挑战，以期为猪遗传改良和医学研究提供参考。

关键词: 猪；养猪业；基因编辑；基因修饰；遗传改良；农业生产；医学研究；新材料

Abstract: Gene editing technology has been demonstrated to have the capacity to target and modify specific locus in the genome of organisms with a high degree of precision. Its utilization in the genetic enhancement of agricultural organisms and biomedical research has been extensive, particularly in the domain of gene editing technology in pigs and the creation of new materials, a field which has undergone a remarkable development. The aim of this paper was to discuss the technological and application progress of gene-edited pigs, and to explore the current situation and challenges in agricultural production, biomedical research and ethical regulation, with a view to providing reference for pig genetic improvement and medical research.

Key words: pig; pig farming industry; gene editing; genetic modification; genetic improvement; agricultural production; medical research; new materials

中图分类号: S828；S814.8

段晓翠，白文娟，史潇靖，周荣，王子帅. 基因编辑猪的应用进展[J]. 中国猪业, 2025, 20(2): 23-34.

参考文献

[1] LUNNEY JK, VAN GOOR A, WALKER KE, et al. Importance of the pig as a human biomedical model[J]. Science Translational Medicine, 2021, 13(621):eabd5758. [2] RUAN JX, XU J, CHEN-TSAI RY, et al. Genome editing in livestock: are we ready for a revolution in animal breeding industry?[J]. Transgenic Research, 2017, 26(6):715-726. [3] DOUDNA JA. The promise and challenge of therapeutic genome editing[J]. Nature, 2020, 578(7794):229-236. [4] WANG SW, GAO C, ZHENG YM, et al. Current applications and future perspective of CRISPR/Cas9 gene editing in cancer[J]. Molecular Cancer, 2022, 21(1):57. [5] JINEK M, CHYLINSKI K, FONFARA I, et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity[J]. Science, 2012, 337(6096):816-821. [6] QI LS, LARSON MH, GILBERT LA, et al. Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression[J]. Cell, 2013, 152(5):1173-1183. [7] GILBERT LA, LARSON MH, MORSUT L, et al. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes[J]. Cell, 2013, 154(2):442-451. [8] WANG T, WEI JJ, SABATINI DM, et al. Genetic screens in human cells using the CRISPR-Cas9 system[J]. Science, 2014, 343(6166):80-84. [9] ABUDAYYEH OO, GOOTENBERG JS, ESSLETZBICHLER P, et al. RNA targeting with CRISPR-cas13[J]. Nature, 2017, 550(7675):280-284. [10] ANZALONE AV, RANDOLPH PB, DAVIS JR, et al. Search-and-replace genome editing without double-strand breaks or donor DNA[J]. Nature, 2019, 576(7785):149-157. [11] CHEN JS, DAGDAS YS, KLEINSTIVER BP, et al. Enhanced proofreading governs CRISPR-Cas9 targeting accuracy[J]. Nature, 2017, 550(7676):407-410. [12] LIU JJ, ORLOVA N, OAKES BL, et al. CasX enzymes comprise a distinct family of RNA-guided genome editors[J]. Nature, 2019, 566(7743):218-223. [13] 张潇筠, 徐坤, 沈俊岑, 等. 一种新型提高HDR效率的CRISPR/Cas9-Gal4BD供体适配基因编辑系统[J]. 遗传, 2022, 44(8):708-719. ZHANG XJ, XU K, SHEN JC, et al. A CRISPR/Cas9-Gal4BD donor adapting system for enhancing homology-directed repair[J]. Hereditas(Beijing), 2022, 44(8):708-719. [14] GIM GM, KWON DH, EOM KH, et al. Production of MSTN-mutated cattle without exogenous gene integration using CRISPR-Cas9[J]. Biotechnology Journal, 2022, 17(7):2100198. [15] 徐奎, 周荣, 牟玉莲, 等. 基因编辑,生命科学领域的一场新革命[J]. 中国猪业, 2016, 11(4):65-66. XU K, ZHOU R, MU YL, et al. Gene editing, a new revolution in the field of life science[J]. China Swine Industry, 2016, 11(4):65-66. [16] FU B, MA H, HUO XP, et al. CRISPR technology acts as a dual-purpose tool in pig breeding: enhancing both agricultural productivity and biomedical applications[J]. Biomolecules, 2024, 14(11):1409. [17] LIU Y, LIU S, SHENG H, et al. Revolutionizing cattle breeding: gene editing advancements for enhancing economic traits[J]. Gene, 2024, 927:148595. [18] ZHANG XM, QIU MY, HAN B, et al. Generation and propagation of high fecundity gene edited fine wool sheep by CRISPR/Cas9[J]. Scientific Reports, 2025, 15(1):2557. [19] 张健, 吴珍芳, 杨化强. CD163基因敲除大白猪的抗蓝耳病性能和主要生产性能研究[J]. 华南农业大学学报, 2023, 44(3):333-339. ZHANG J, WU ZF , YANG HQ. Resistance to blue ear disease and production performance assessment of CD163 gene-edited Large White pigs.[J]. Journal of South China Agricultural University, 2023, 44(3):333-339. [20] 徐鑫, 刘明军. CRISPR/Cas9基因编辑技术在绵羊中的应用研究进展[J]. 中国畜牧兽医, 2022, 49(11):4129-4138. XU X, LIU MJ. Research progress on application of CRISPR/Cas9 genome editing systems in sheep[J]. China Animal Husbandry & Veterinary Medicine, 2022, 49(11):4129-4138. [21] 王莎莎, 朱辉斌, 卢晟盛, 等. FAH基因敲除克隆小型猪的制备及繁育[J]. 中国比较医学杂志, 2019, 29(5):29-37. WANG SS, ZHU HB, LU SS, et al. Generation and breeding of FAH gene knockout cloned minipigs[J]. Chinese Journal of Comparative Medicine, 2019, 29(5):29-37. [22] MORELLI KH, WU Q, GOSZTYLA ML, et al. An RNA-targeting CRISPR-Cas13d system alleviates disease-related phenotypes in Huntington's disease models[J]. Nature Neuroscience, 2023, 26(1):27-38. [23] JIN X, SIMMONS SK, GUO A, et al. In vivo Perturb-Seq reveals neuronal and glial abnormalities associated with autism risk genes[J]. Science, 2020, 370(6520):eaaz6063. [24] KLANN TS, BLACK JB, CHELLAPPAN M, et al. CRISPR-Cas9 epigenome editing enables high-throughput screening for functional regulatory elements in the human genome[J]. Nature Biotechnology, 2017, 35(6):561-568. [25] ISHII T. Germline genome-editing research and its socioethical implications[J]. Trends in Molecular Medicine, 2015, 21(8):473-481. [26] 许美娜, 朱奕舟, 林思远, 等. CRISPR/Cas9基因编辑技术在猪育种中的研究进展[J]. 广东农业科学, 2022, 49(8):87-96. XU MN, ZHU YZ, LIN SY, et al. Progress of the application of CRISPR/Cas9 gene editing technology in pig breeding[J]. Guangdong Agricultural Sciences, 2022, 49(8):87-96. [27] SHI X, TANG T, LIN QY, et al. Efficient generation of bone morphogenetic protein 15-edited Yorkshire pigs using CRISPR/Cas9[J]. Biology of Reproduction, 2020, 103(5):1054-1068. [28] LIU Y, YANG YL, LI WT, et al. NRDR inhibits estradiol synthesis and is associated with changes in reproductive traits in pigs[J]. Molecular Reproduction and Development, 2019, 86(1):63-74. [29] 曹随忠, 岳成鹤, 李西睿, 等. 锌指核酸酶技术制备肌肉生长抑制素基因敲除的五指山小型猪成纤维细胞[J]. 遗传, 2013, 35(6):778-785. CAO SZ, YUE CH, LI XR, et al. Production of myostatin gene knockout Wuzhishan miniature pig fibroblasts with zinc-finger nucleases[J]. Hereditas(Beijing), 2013, 35(6):778-785. [30] 崔文涛, 谢珊珊, 李想, 等. 通过ZFN技术编辑猪MSTN基因创制高瘦肉率梅山猪新种质[J]. 农业生物技术学报, 2019, 27(12):2272-2280. CUI WT, XIE SS, LI X, et al. New germplasm of Meishan pig(sus scrofa) with high lean-meat rate was created by editing pig MSTN gene with ZFN technique[J]. Journal of Agricultural Biotechnology, 2019, 27(12):2272-2280. [31] LI RQ, ZENG W, MA M, et al. Precise editing of myostatin signal peptide by CRISPR/Cas9 increases the muscle mass of Liang Guang Small Spotted pigs[J]. Transgenic Research, 2020, 29(1):149-163. [32] XIANG GH, REN JL, HAI T, et al. Editing porcine IGF2 regulatory element improved meat production in Chinese Bama pigs[J]. Cellular and Molecular Life Sciences, 2018, 75(24):4619-4628. [33] DUO TQ, LIU XH, MO DL, et al. Single-base editing in IGF2 improves meat production and intramuscular fat deposition in Liang Guang Small Spotted pigs[J]. Journal of Animal Science and Biotechnology, 2024, 15(1). doi: 10.1186/s40104-023-00930-4. [34] LI WT, WU KL, LIU Y, et al. Molecular cloning of SLC35D3 and analysis of its role during porcine intramuscular preadipocyte differentiation[J]. BMC Genetics, 2020, 21(1):20. [35] LI WT, YANG YL, LIU Y, et al. Integrated analysis of mRNA and miRNA expression profiles in livers of Yimeng black pigs with extreme phenotypes for backfat thickness[J]. Oncotarget, 2017, 8(70):114787-114800. [36] LIU Z, WU T, XIANG G, et al. Enhancing animal sisease resistance, production efficiency, and welfare through precise genome editing[J]. International Journal of Molecular Sciences, 2022, 23(13):7331. [37] XU K, ZHOU YR, MU YL, et al. CD163 and pAPN double-knockout pigs are resistant to PRRSV and TGEV and exhibit decreased susceptibility to PDCoV while maintaining normal production performance[J]. eLife, 2020, 9:e57132. [38] AFE AE, SHEN ZJ, GUO X, et al. African swine fever virus interaction with host innate immune factors[J]. Viruses, 2023, 15(6):1220. [39] SHEN ZJ, JIA H, XIE CD, et al. Bayesian phylodynamic analysis reveals the dispersal patterns of african swine fever virus[J]. Viruses, 2022, 14(5):889. [40] ZHENG ZZ, XU L, GAO YB, et al. Testing multiplexed anti-ASFV CRISPR-Cas9 in reducing African swine fever virus[J]. Microbiology Spectrum, 2024, 12(7):e0216423. [41] ZHENG QT, LIN J, HUANG JJ, et al. Reconstitution of UCP1 using CRISPR/Cas9 in the white adipose tissue of pigs decreases fat deposition and improves thermogenic capacity[J]. Proceedings of the National Academy of Sciences of the United States of America, 2017, 114(45):9474-9482. [42] GUO XR, FAN XH, XIE CD, et al. Suppressing IGF2R mitigates hypoxia-induced apoptosis by reducing the expression of pro-apoptotic factor BAX[J]. International Journal of Biological Macromolecules, 2025, 284(Pt1):137785. [43] PENG J, WANG Y, JIANG JY, et al. Production of human albumin in pigs through CRISPR/Cas9-mediated knockin of human cDNA into swine albumin locus in the zygotes[J]. Scientific Reports, 2015, 5:16705. [44] NIU D, MA X, YUAN TY, et al. Porcine genome engineering for xenotransplantation[J]. Advanced Drug Delivery Reviews, 2021, 168:229-245. [45] YAN S, TU ZC, LIU ZM, et al. A huntingtin knockin pig model recapitulates features of selective neurodegeneration in Huntington’s disease[J]. Cell, 2018, 173(4):989-1002. [46] ZHOU XQ, XIN JG, FAN NN, et al. Generation of CRISPR/Cas9-mediated gene-targeted pigs via somatic cell nuclear transfer[J]. Cellular and Molecular Life Sciences, 2015, 72(6):1175-1184. [47] 朱文娟, 辛磊磊, 李晨晓, 等. 小型猪2型糖尿病模型研究进展[J]. 实验动物科学, 2016, 33(3):61-65. ZHU WJ, XIN LL, LI CX, et al. Study advance on type 2 diabetes mellitus model in miniature pigs[J]. Laboratory Animal Science, 2016, 33(3):61-65. [48] 杨述林, 张凯艺, 朱文娟, 等. 小型猪2型糖尿病模型的构建方法及应用[P]. 中国: CN110305872A, 2019-10-08. YANG SL, ZHANG KY, ZHU WJ, et al. Construction method and application of minipig type 2 diabetes model[P]. China: CN110305872A, 2019-10-08. [49] HUANG L, HUA ZD, XIAO HW, et al. CRISPR/Cas9-mediated ApoE-/ - and LDLR-/ - double gene knockout in pigs elevates serum LDL-C and TC levels[J]. Oncotarget, 2017, 8(23):37751-37760. [50] SUZUKI S, IWAMOTO M, HASHIMOTO M, et al. Generation and characterization of RAG2 knockout pigs as animal model for severe combined immunodeficiency[J]. Veterinary Immunology and Immunopathology, 2016, 178:37-49. [51] LIU XY, LI GL, LIU Y, et al. Advances in CRISPR/Cas gene therapy for inborn errors of immunity[J]. Frontiers in Immunology, 2023, 14:1111777. [52] JOSHI K, TELUGU BP, PRATHER RS, et al. Benefits and opportunities of the transgenic Oncopig cancer model[J]. Trends in Cancer, 2024, 10(3):182-184. [53] WANG KP, JIN Q, RUAN DG, et al. Cre-dependent Cas9-expressing pigs enable efficient in vivo genome editing[J]. Genome Research, 2017, 27(12):2061-2071. [54] VROLYK V, DESMARAIS MJ, LAMBERT D, et al. Neonatal and juvenile ocular development in g?ttingen minipigs and domestic pigs: a histomorphological and immunohistochemical study[J]. Veterinary Pathology, 2020, 57(6):889-914. [55] KOSTIC C, LILLICO SG, CRIPPA SV, et al. Rapid cohort generation and analysis of disease spectrum of large animal model of cone dystrophy[J]. PLoS One, 2013, 8(8):e71363. [56] SOMMER JR, ESTRADA JL, COLLINS EB, et al. Production of ELOVL4 transgenic pigs: a large animal model for stargardt-like macular degeneration[J]. The British Journal of Ophthalmology, 2011, 95(12):1749-1754. [57] MORETTI A, FONTEYNE L, GIESERT F, et al. Somatic gene editing ameliorates skeletal and cardiac muscle failure in pig and human models of Duchenne muscular dystrophy[J]. Nature Medicine, 2020, 26(2):207-214. [58] DUQUE SI, ARNOLD WD, ODERMATT P, et al. A large animal model of spinal muscular atrophy and correction of phenotype[J]. Annals of Neurology, 2015, 77(3):399-414. [59] MOHIUDDIN MM, SINGH AK, SCOBIE L, et al. Graft dysfunction in compassionate use of genetically engineered pig-to-human cardiac xenotransplantation: a case report[J]. Lancet, 2023, 402(10399):397-410. [60] 程新宇. 动物基因编辑的若干伦理问题及其治理[J]. 华中科技大学学报(社会科学版), 2022, 36(5):9-16. CHENG XY. Ethical issues and its governance in animal gene editing[J]. Journal of Huazhong University of Science and Technology(Social Science Edition), 2022, 36(5):9-16. [61] 章德宾, 罗瑶, 陈文进. 基因编辑技术发展现状[J]. 生物工程学报, 2020, 36(11):2345-2356. ZHANG DB, LUO Y, CHEN WJ. Current development of gene editing[J]. Chinese Journal of Biotechnology, 2020, 36(11):2345-2356. [62] CENGIZ N, WAREHAM CS. Ethical considerations in xenotransplantation: a review[J]. Current Opinion in Organ Transplantation, 2020, 25(5):483-488. [63] LIU YP, QIN LX, TONG RS, et al. Regulatory changes in China on xenotransplantation and related products[J]. Xenotransplantation, 2020, 27(3):e12601. [64] 刘佳. CRISPR/Cas9基因编辑技术的生物伦理和法律问题[J]. 分子植物育种, 2024, 22(10):3188-3194. LIU J. Bioethical and legal issues of CRISPR/Cas9 gene editing technology[J]. Molecular Plant Breeding, 2024, 22(10):3188-3194. [65] TARABEIH M, AMIEL A, NA’AMNIH W. The view of the three monotheistic religions toward xenotransplantation[J]. Clinical Transplantation, 2024, 38(1):e15192. [66] 李奎, 王小龙, 樊自尧. 基因组编辑农业动物及其管理的共识[J]. 中国农业科学, 2020, 53(9):1920. LI K, WANG XL, FAN ZY. Consensus on genome editing of agricultural animals and their management[J]. Scientia Agricultura Sinica, 2020, 53(9):1920. [67] 吴添文, 齐传翔, 李训碧, 等. 基因组编辑猪的研究现状及展望[J]. 农业生物技术学报, 2017, 25(5):781-787. WU TW, QI CX, LI XB, et al. Research progress and prospects of genome editing pigs(sus scrofa)[J]. Journal of Agricultural Biotechnology, 2017, 25(5):781-787. [68] LUO JJ, BIAN CW, LIU M, et al. Research on gene editing and immunosuppressants in kidney xenotransplantation[J]. Transplant Immunology, 2025, 89:102184.

Metrics

Viewed

Full text

Abstract

Cited

Shared

Discussed