家养动物抗病基因挖掘与新材料创制研究进展

doi:10.3969/j.issn.1674-7968.2026.02.001

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Abstract Disease resistance breeding in domestic animals is crucial for safeguarding the healthy development of the livestock industry and ensuring public health security. With the rapid advancement of high-throughput screening (HTS) technologies, the mining of disease resistance genes has entered a precision- and efficiency-oriented genomics era. This review systematically summarizes the principles and workflows involved in screening for disease resistance genes in domestic animals using core HTS technologies, including CRISPR-Cas9, RNA interference (RNAi), transcriptome analysis, protein interactomics, and epigenomics. It elaborates on the functional diversity of resistance genes identified through these techniques, classifying them into seven categories based on their mechanisms of action: Innate immune response, adaptive immune response, programmed cell death, viral adhesion and entry, intracellular trafficking, viral replication, and immune evasion. Furthermore, the article summarizes successful cases of creating novel disease-resistant materials and analyzes current challenges faced by HTS, such as off-target effects, efficiency problems, and data analysis complexity. Finally, the review prospects future directions involving interdisciplinary integration, technological optimization, and clinical translation, aiming to provide comprehensive theoretical references and technical pathways for disease resistance breeding research in domestic animals.

Key words： High-throughput screening Domestic animals Disease resistance breeding

Received: 03 October 2025

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Corresponding Authors: ^* yaofengzhao@cau.edu.cn

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	HU Si-Yu
	ZHANG Ran
	ZHAO Yao-Feng

Cite this article:

HU Si-Yu,ZHANG Ran,ZHAO Yao-Feng. Research Progress on Mining Disease Resistance Genes and Creating New Materials in Domestic Animals[J]. 农业生物技术学报, 2026, 34(2): 229-244.

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https://journal05.magtech.org.cn/Jwk_ny/EN/10.3969/j.issn.1674-7968.2026.02.001 OR https://journal05.magtech.org.cn/Jwk_ny/EN/Y2026/V34/I2/229

[1] 李欣, 刘旭霞, 张文斐. 2023. 全球农业基因编辑技术监管动态及发展趋势[J]. 生命科学, 35(2): 114-122.
(Li X, Liu X X, Zhang W F.2023. Supervision dynamic and development tendency of global agricultural gene editing technology[J]. Chinese Bulletin of Life Sciences, 35(2): 114-122.)
[2] 庄重, 赵龙, 白皓, 等. 2022. CRISPR/Cas9技术在家禽育种方面的应用[J]. 中国农业科技导报, 24(1): 14-23.
(Zhuang Z, Zhao L, Bai H, et al.2022. Development of CRISPR/Cas9 and its application in poultry[J]. Journal of Agricultural Science and Technology, 24(1): 14-23.)
[3] Dekeyzer B, Hoareau M, Laghlali G, et al.2018. Utiliser le système CRISPR/Cas9 SAM (synergic activation mediator) pour identifier des facteurs de restriction antiviraux par criblage génomique[J]. Médecine/Sciences, 34(5): 401-403.
[4] Alda-Catalinas C, Bredikhin D, Hernando-Herraez I, et al.2020. A Single-cell transcriptomics CRISPR-activation screen identifies epigenetic regulators of the zygotic genome activation program[J]. Cell Systems, 11: 25-41.
[5] Badaoui B, Rutigliano T, Anselmo A, et al.2014. RNA-sequence analysis of primary alveolar macrophages after in vitro infection with Porcine reproductive and respiratory syndrome virus strains of differing virulence[J]. PLOS ONE, 9(3): e91918.
[6] Burger B T, Beaton B P, Campbell M A, et al.2024. Generation of a commercial-scale founder population of porcine reproductive and Respiratory syndrome virus resistant pigs using CRISPR-Cas[J]. The CRISPR Journal, 7(1): 12-28.
[7] Calvert J G, Slade D E, Shields S L, et al.2007. CD163 expression confers susceptibility to Porcine reproductive and respiratory syndrome viruses[J]. Journal of Virology, 81(14): 7371-7379.
[8] Carpenter A E, Sabatini D M.2004. Systematic genome-wide screens of gene function[J]. Nature Reviews Genetics, 5: 11-22.
[9] Chen B H, Xie Y S, He Z, et al.2025. THAP11-mediated K48- and K63-linked ubiquitination is essential for the degradation of Porcine reproductive and respiratory syndrome virus nonstructural protein 1β[J]. Cellular and Molecular Life Sciences, 82: 246.
[10] Chen P R, Rowland R R R, Stoian A M, et al.2022. Disruption of anthrax toxin receptor 1 in pigs leads to a rare disease phenotype and protection from Senecavirus A infection[J]. Scientific Reports, 12: 5009.
[11] Conesa A, Madrigal P, Tarazona S, et al.2016. A survey of best practices for RNA-seq data analysis[J]. Genome Biology, 17: 13.
[12] Ding S, Diep J, Feng N G, et al.2018. STAG2 deficiency induces interferon responses via cGAS-STING pathway and restricts virus infection[J]. Nature Communications, 9: 1485.
[13] Dolata K M, Fuchs W, Caignard G, et al.2023. CP204L is a multifunctional protein of African swine fever virus that interacts with the VPS39 subunit of the homotypic fusion and vacuole protein sorting complex and promotes lysosome clustering[J]. Journal of Virology, 97(2): e0194322.
[14] Dzimianski J V, Scholte F E M, Bergeron E, et al.2019. ISG15: It's complicated[J]. Journal of Molecular Biology, 431: 4203-4216.
[15] Echeverri C J, Perrimon N.2006. High-throughput RNAi screening in cultured cells: A user's guide[J]. Nature Reviews Genetics, 7(5): 373-384.
[16] Fedorov Y, Anderson E M, Birmingham A, et al.2006. Off-target effects by siRNA can induce toxic phenotype[J]. RNA, 12: 1188-1196.
[17] Gilbert L A, Horlbeck M A, Adamson B, et al.2014. Genome-scale CRISPR-mediated control of gene repression and activation[J]. Cell, 159(3): 647-661.
[18] Günther J, Esch K, Poschadel N, et al.2011. Comparative kinetics of Escherichia coli- and Staphylococcus aureus-specific activation of key immune pathways in mammary epithelial cells demonstrates that S. aureus elicits a delayed response dominated by interleukin-6 (IL-6) but not by IL-1A or tumor necrosis factor alpha[J]. Infection and Immunity, 79(2): 695-707.
[19] Han J, Perez J T, Chen C, et al.2018. Genome-wide CRISPR/Cas9 screen identifies host factors essential for influenza virus replication[J]. Cell Reports, 23(2): 596-607.
[20] Haque A, Engel J, Teichmann S A, et al.2017. A practical guide to single-cell RNA-sequencing for biomedical research and clinical applications[J]. Genome Medicine, 9: 75.
[21] Heaton B E, Kennedy E M, Dumm R E, et al.2017. A CRISPR activation screen identifies a pan-avian influenza virus inhibitory host factor[J]. Cell Reports, 20: 1503-1512.
[22] Hölper J E, Grey F, Baillie J K, et al.2021. A genome-wide CRISPR/Cas9 screen reveals the requirement of host sphingomyelin synthase 1 for infection with Pseudorabies virus mutant gD-Pass[J]. Viruses, 13(8): 1574.
[23] Housden B E, Perrimon N.2016. Comparing CRISPR and RNAi-based screening technologies[J]. Nature Biotechnology, 34(6): 621-623.
[24] Hu S J, Gan M L, Wei Z, et al.2024. Identification of host factors for livestock and poultry viruses: Genome-wide screening technology based on the CRISPR system[J]. Frontiers in Microbiology, 15: 1498641.
[25] Idoko-Akoh A, Goldhill D H, Sheppard C M, et al.2023. Creating resistance to avian influenza infection through genome editing of the ANP32 gene family[J]. Nature Communications, 14: 6136.
[26] Jiang J H, Sun Y M, Wang Y L, et al.2022. Genome-wide CRISPR/Cas9 screen identifies host factors important for Porcine reproductive and respiratory syndrome virus replication[J]. Virus Research, 314: 198738.
[27] Kaelin W G.2012. Use and abuse of RNAi to study mammalian gene function[J]. Science, 337(6093): 421-422.
[28] Konermann S, Brigham M D, Trevino A E, et al.2014. Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex[J]. Nature, 517(7536): 583-588.
[29] Langfelder P, Horvath S.2008. WGCNA: An R package for weighted correlation network analysis[J]. BMC Bioinformatics, 9: 559.
[30] Li D, Wu P X, Liu H N, et al.2021. A QP509L/QP383R-deleted African swine fever virus is highly attenuated in swine but does not confer protection against parental virus challenge[J]. Journal of Virology, 96(1): e0150021.
[31] Liang G, Duan X Y, Li J, et al.2025. YIPF5 is an essential host factor for Porcine epidemic diarrhea virus double-membrane vesicle formation[J]. Journal of Virology, 99(6): e0032025.
[32] Lin Y, Li J, Li C, et al.2022. Application of CRISPR/Cas9 system in establishing large animal models[J]. Frontiers in Cell and Developmental Biology, 10: 919155.
[33] Luo Y, Tan C W, Xie S Z, et al.2021. Identification of ZDHHC17 as a potential drug target for Swine acute diarrhea syndrome coronavirus infection[J]. mBio, 12(5): e0234221.
[34] Ma H M, Adams L J, Raju S, et al.2024. The low-density lipoprotein receptor promotes infection of multiple encephalitic alphaviruses[J]. Nature Communications, 15: 246.
[35] Matia A, Lorenzo M M, Romero-Estremera Y, et al.2022. Identification of beta2 microglobulin, the product of B2M gene, as a host factor for Vaccinia virus infection by genome-wide CRISPR genetic screens[J]. PLOS Pathogens, 18(12): e1010800.
[36] McCleary S, Strong R, McCarthy R R, et al.2020. Substitution of warthog NF-κB motifs into RELA of domestic pigs is not sufficient to confer resilience to African swine fever virus[J]. Scientific Reports, 10: 8951.
[37] Miles L A, Burga L N, Gardner E E, et al.2017. Anthrax toxin receptor 1 is the cellular receptor for Seneca Valley virus[J]. Journal of Clinical Investigation, 127(8): 2957-2967.
[38] Mon K K Z, Kern C, Chanthavixay G, et al.2021. Tolerogenic immunoregulation towards Salmonella enteritidis contributes to colonization persistence in young chicks[J]. Infection and Immunity, 89(8): e0073620.
[39] Mortazavi A, Williams B A, Mccue K, et al.2008. Mapping and quantifying mammalian transcriptomes by RNA-Seq[J]. Nature Methods, 5(7): 621-628.
[40] Munir M, Embry A, Doench J G, et al.2024. Genome-wide CRISPR activation screen identifies JADE3 as an antiviral activator of NF-kB-dependent IFITM3 expression[J]. Journal of Biological Chemistry, 300(4): 107153.
[41] Pan Z Y, Yao Y L, Yin H W, et al.2021. Pig genome functional annotation enhances the biological interpretation of complex traits and human disease[J]. Nature Communications, 12: 5848.
[42] Pannhorst K, Carlson J, Holper J E, et al.2023. The non-classical major histocompatibility complex Ⅱ protein SLA-DM is crucial for African swine fever virus replication[J]. Scientific Reports, 13(1): 10342.
[43] Paul A, Muralidharan A, Biswas A, et al.2022. siRNA therapeutics and its challenges: Recent advances in effective delivery for cancer therapy[J]. OpenNano, 7: 100063.
[44] Peng G C, Liu T R, Qi X L, et al.2024. A genome-wide CRISPR screening uncovers that TOB1 acts as a key host factor for FMDV infection via both IFN and EGFR mediated pathways[J]. PLOS Pathogens, 20(3): e1012104.
[45] Pławińska-Czarnak J, Majewska A, Zarzyńska J M, et al.2025. The gene expression profile of milk somatic cells of small ruminant Lentivirus-seropositive and -seronegative dairy goats (Capra hircus) during their first lactation[J]. Viruses, 17(7): 944.
[46] Rola-Łuszczak M, Materniak-Kornas M, Pluta A, et al.2018. Transcriptional profiles of PBMCs from pigs infected with three genetically diverse porcine reproductive and Respiratory syndrome virus strains[J]. Molecular Biology Reports, 45: 675-688.
[47] Schokker D, Peters T H F, Hoekman A J W, et al.2012. Differences in the early response of hatchlings of different chicken breeding lines to Salmonella enterica serovar Enteritidis infection[J]. Poultry Science, 91: 346-353.
[48] Shalem O, Sanjana N E, Hartenian E, et al.2013. Genome-scale CRISPR-Cas9 knockout screening in human cells[J]. Science, 343(6166): 84-87.
[49] Shen H H, Zhao Q, Wen Y P, et al.2023. Porcine reproductive and respiratory syndrome virus upregulates SMPDL3B to promote viral replication by modulating lipid metabolism[J]. iScience, 26: 107450.
[50] Shi X N, Zhang Y F, Chen S X, et al.2024. Differential gene expression and immune cell infiltration in maedi-visna virus-infected lung tissues[J]. BMC Genomics, 25: 534.
[51] Song Y M, Huang H X, Hu Y Z, et al.2021. A genome-wide CRISPR/Cas9 gene knockout screen identifies immunoglobulin superfamily DCC subclass member 4 as a key host factor that promotes influenza virus endocytosis[J]. PLOS Pathogens, 17(12): e1010141.
[52] Spring W F, Tan E G, Rong I, et al.2024. Validation of candidate host cell entry factors for Bovine herpes virus type-1 based on a genome-wide CRISPR knockout screen[J]. Viruses, 16: 297.
[53] Sun L M, Zhao C Z, Fu Z, et al.2021. Genome-scale CRISPR screen identifies TMEM41B as a multi-function host factor required for Coronavirus replication[J]. PLoS Pathogens, 17(12): e1010113.
[54] Tan W S, Rong E, Dry I, et al.2023. GARP and EARP are required for efficient BoHV-1 replication as identified by a genome wide CRISPR knockout screen[J]. PLOS Pathogens, 19(12): e1011822.
[55] Tang F C, Barbacioru C, Wang Y Z, et al.2009. mRNA-seq whole-transcriptome analysis of a single cell[J]. Nature Methods, 6(5): 377-382.
[56] Thamamongood T, Aebischer A, Wagner V, et al.2020. A genome-wide CRISPR-Cas9 screen reveals the requirement of host cell sulfation for Schmallenberg virus infection[J]. Journal of Virology, 94(17): e0075220.
[57] Vu T H, Kim C, Truong A D, et al.2025. Unveiling the role of long non-coding RNAs in chicken immune response to highly pathogenic avian influenza H5N1 infection[J]. Poultry Science, 104(1): 104524.
[58] Wang G W, Jiang L, Wang J L, et al.2025. Genome-wide siRNA library screening identifies human host factors that influence the replication of the highly pathogenic H5N1 influenza virus[J]. mLife, 4(1): 55-69.
[59] Wang J R, Liu H L, Yang Y Q, et al.2023a. Genome-scale CRISPR screen identifies TRIM2 and SLC35A1 associated with Porcine epidemic diarrhoea virus infection[J]. International Journal of Biological Macromolecules, 250: 125962.
[60] Wang T, Zhang J J, Wang Y L, et al.2023b. Influenza-trained mucosal-resident alveolar macrophages confer long-term antitumor immunity in the lungs[J]. Nature Immunology, 24: 423-438.
[61] Wang X L, Jin Q, Xiao W W, et al.2022. Genome-wide CRISPR/Cas9 screen reveals a role for SLC35A1 in the adsorption of Porcine deltacoronavirus[J]. Journal of Virology, 96(24): e0162622.
[62] Wang Z, Gerstein M, Snyder M.2009. RNA-Seq: A revolutionary tool for transcriptomics[J]. Nature Reviews Genetics, 10: 57.
[63] Whitworth K M, Rowland R R R, Ewen C L, et al.2015. Gene-edited pigs are protected from Porcine reproductive and respiratory syndrome virus[J]. Nature Biotechnology, 34: 1-3.
[64] Whitworth K M, Rowland R R R, Petrovan V, et al.2019. Resistance to coronavirus infection in amino peptidase N-deficient pigs[J]. Transgenic Research, 28: 21-32.
[65] Workman A M, Heaton M P, Vander Ley B L, et al.2023. First gene-edited calf with reduced susceptibility to a major viral pathogen[J]. PNAS Nexus, 2(5): 1-14.
[66] Workman A M, Heaton M P, Vander Ley B L.2025. CD46 gene editing confers ex vivo BVDV resistance in fibroblasts from cloned angus calves[J]. Viruses, 17: 775.
[67] Wu H, Wang Y, Zhang Y, et al.2015. TALE nickase-mediated SP110 knockin endows cattle with increased resistance to tuberculosis[J]. Proceedings of the National Academy of Sciences, 112: E1530-E1539.
[68] Xu K, Zhou Y, Mu Y, et al.2020. 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, 9: e57132.
[69] Xue C, Greene E C.2021. DNA repair pathway choices in CRISPR-Cas9-mediated genome editing[J]. Trends in Genetics, 37(7): 639-656.
[70] Yi C Y, Cai C, Cheng Z, et al.2022. Genome-wide CRISPR-Cas9 screening identifies the CYTH2 host gene as a potential therapeutic target of influenza viral infection[J]. Cell Reports, 38(13): 110559.
[71] Zhang B, Horvath S.2005. A general framework for weighted gene co-expression network analysis[J]. Statistical Applications in Genetics & Molecular Biology, 4(1): 17.
[72] Zhang H G, Li X, Wang Y W, et al.2023. Genome-wide CRISPR/Cas9 screening identifies that mitochondrial solute carrier SLC25A23 attenuates type I IFN antiviral immunity via interfering with MAVS aggregation[J]. Journal of Immunology, 211(9): 1406-1417.
[73] Zhang J, Rodríguez F, Navas M J, et al.2020. Fecal microbiota transplantation from warthog to pig confirms the influence of the gut microbiota on African swine fever susceptibility[J]. Scientific Reports, 10: 17605.
[74] Zhao C Z, Liu H L, Xiao T H, et al.2020. CRISPR screening of porcine sgRNA library identifies host factors associated with Japanese encephalitis virus replication[J]. Nature Communications, 11(1): 5178.
[75] Zhao Y J, Yuan J L, Xiao D, et al.2023. HSP90AB1 is a host factor that promotes Porcine deltacoronavirus replication[J]. Journal of Biological Chemistry, 300(1): 105536.
[76] Zhou A, Zhang W H, Dong X, et al.2021. Porcine genome-wide CRISPR screen identifies the Golgi apparatus complex protein COG8 as a pivotal regulator of influenza virus infection[J]. The CRISPR Journal, 4(6): 872-883.
[77] Zhou J L, Feng Z H, Lv D Y, et al.2024. Unveiling the role of protein kinase C θ in Porcine epidemic diarrhea virus replication: Insights from genome-wide CRISPR/Cas9 library screening[J]. International Journal of Molecular Sciences, 25(6): 3096.
[78] Zheng Z, Xu L, Gao Y, et al.2024. Testing multiplexed anti-ASFV CRISPR-Cas9 in reducing African swine fever virus[J]. Microbiology Spectrum, 12(7): e0216423.
[79] Zuo Q S, Wang Y J, Cheng S Z, et al.2016. Site-directed genome knockout in chicken cell line and embryos can use CRISPR/Cas gene editing technology[J]. G3 (Bethesda), 6: 1787-1792.