{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T05:48:43Z","timestamp":1771480123783,"version":"3.50.1"},"reference-count":182,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Universities of Spain","award":["2021-067\/PN\/MS-RECUAL\/CD"],"award-info":[{"award-number":["2021-067\/PN\/MS-RECUAL\/CD"]}]},{"name":"Ministry of Universities of Spain","award":["UCA\/REC64VIT\/2024"],"award-info":[{"award-number":["UCA\/REC64VIT\/2024"]}]},{"DOI":"10.13039\/501100008723","name":"University of Cadiz","doi-asserted-by":"publisher","award":["2021-067\/PN\/MS-RECUAL\/CD"],"award-info":[{"award-number":["2021-067\/PN\/MS-RECUAL\/CD"]}],"id":[{"id":"10.13039\/501100008723","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008723","name":"University of Cadiz","doi-asserted-by":"publisher","award":["UCA\/REC64VIT\/2024"],"award-info":[{"award-number":["UCA\/REC64VIT\/2024"]}],"id":[{"id":"10.13039\/501100008723","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Biotechnological advances applied to the generation of genetically modified (GM) animals have shown the potential to develop innovative solutions for different challenges in key areas such as agriculture and human medicine. Despite its enormous potential, the deployment of genetic modification in animals, and its subsequent commercialization, does not meet the same public acceptance as GM plant-derived products, which are currently widely adopted around the world. In this review, we highlight the main examples of GM and gene-edited animal-derived products already approved by the FDA and discuss the regulatory context inherent to such processes, including the risk-based assessment analysis based on a case-by-case evaluation. Moreover, cases of GM animals already approved by other jurisdictions around the world are also discussed.<\/jats:p>","DOI":"10.3390\/ani15111570","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T11:12:57Z","timestamp":1748344377000},"page":"1570","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genetically Modified Animal-Derived Products: From Regulations to Applications"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9403-2211","authenticated-orcid":false,"given":"Carlos","family":"Fajardo","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Marine and Environmental Sciences, Instituto Universitario de Investigaci\u00f3n Marina (INMAR), Campus de Excelencia Internacional del Mar (CEI\u00b7MAR), University of Cadiz (UCA), 11510 Puerto Real, Spain"},{"name":"Interdisciplinary Centre of Marine and Environmental Research, University of Porto (CIIMAR), 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9470-0509","authenticated-orcid":false,"given":"Marta","family":"Macedo","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research, University of Porto (CIIMAR), 4450-208 Matosinhos, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto (UP), 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0305-8174","authenticated-orcid":false,"given":"Tonka","family":"Buha","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research, University of Porto (CIIMAR), 4450-208 Matosinhos, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto (UP), 4050-313 Porto, Portugal"},{"name":"SPAROS Lda., \u00c1rea Empresarial de Marim, Lote C, 8700-221 Olh\u00e3o, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8860-6020","authenticated-orcid":false,"given":"Marcos","family":"De Donato","sequence":"additional","affiliation":[{"name":"Center for Aquaculture Technologies (CAT), San Diego, CA 92121, USA"},{"name":"Escuela de Medicina y Ciencias de la Salud, Tecnol\u00f3gico de Monterrey, Quer\u00e9taro 76130, Mexico"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3758-0849","authenticated-orcid":false,"given":"Benjamin","family":"Costas","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research, University of Porto (CIIMAR), 4450-208 Matosinhos, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto (UP), 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0751-5966","authenticated-orcid":false,"given":"Juan Miguel","family":"Mancera","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Marine and Environmental Sciences, Instituto Universitario de Investigaci\u00f3n Marina (INMAR), Campus de Excelencia Internacional del Mar (CEI\u00b7MAR), University of Cadiz (UCA), 11510 Puerto Real, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/nature01019","article-title":"Evolution, Consequences and Future of Plant and Animal Domestication","volume":"418","author":"Diamond","year":"2002","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lawrence, T.L.J., Fowler, V.R., and Novakofski, J.E. (2012). General Aspects of Growth, CABI.","DOI":"10.1079\/9781780641461.0001"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1073\/pnas.0809798106","article-title":"Domestication and Growth Hormone Transgenesis Cause Similar Changes in Gene Expression in Coho Salmon (Oncorhynchus kisutch)","volume":"106","author":"Devlin","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/s41576-020-0227-y","article-title":"Harnessing Genomics to Fast-Track Genetic Improvement in Aquaculture","volume":"21","author":"Houston","year":"2020","journal-title":"Nat. Rev. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1073\/pnas.2202184119","article-title":"Biotechnology Can Help Us Save the Genetic Heritage of Salmon and Other Aquatic Species","volume":"119","author":"Fedoroff","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Turnbull, C., Lillemo, M., and Hvoslef-Eide, T.A.K. (2021). Global Regulation of Genetically Modified Crops Amid the Gene Edited Crop Boom\u2014A Review. Front. Plant Sci., 12.","DOI":"10.3389\/fpls.2021.630396"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"74","DOI":"10.4161\/gmcr.24176","article-title":"The Global Income and Production Effects of Genetically Modified (GM) Crops 1996-2011","volume":"4","author":"Brookes","year":"2013","journal-title":"GM Crops Food"},{"key":"ref_8","unstructured":"Lichtfouse, E. (2017). World Cultivation of Genetically Modified Crops: Opportunities and Risks BT\u2014Sustainable Agriculture Reviews, Springer International Publishing."},{"key":"ref_9","unstructured":"ISAAA (2025, May 15). Executive Summary Biotech Crops Drive Socio-Economic Development and Sustainable Environment in the New Frontier. Available online: https:\/\/www.isaaa.org\/resources\/publications\/briefs\/55\/executivesummary\/default.asp."},{"key":"ref_10","unstructured":"ISAAA (2025, May 15). Global Status of Commercialized Biotech\/GM Crops in 2018. Available online: https:\/\/www.isaaa.org\/resources\/publications\/briefs\/54\/."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.tifs.2015.05.001","article-title":"Genetically Modified Animals: Options and Issues for Traceability and Enforcement","volume":"44","author":"Lievens","year":"2015","journal-title":"Trends Food Sci. Technol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/315680a0","article-title":"Production of Transgenic Rabbits, Sheep and Pigs by Microinjection","volume":"315","author":"Hammer","year":"1985","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/89313","article-title":"Deletion of the Alpha(1,3)Galactosyl Transferase (GGTA1) Gene and the Prion Protein (PrP) Gene in Sheep","volume":"19","author":"Denning","year":"2001","journal-title":"Nat. Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1126\/science.1198020","article-title":"Suppression of Avian Influenza Transmission in Genetically Modified Chickens","volume":"331","author":"Lyall","year":"2011","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/nbt1271","article-title":"Production of Cattle Lacking Prion Protein","volume":"25","author":"Richt","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/nbt1198","article-title":"Generation of Cloned Transgenic Pigs Rich in Omega-3 Fatty Acids","volume":"24","author":"Lai","year":"2006","journal-title":"Nat. Biotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6361","DOI":"10.1073\/pnas.0308111101","article-title":"Functional Expression of a Delta12 Fatty Acid Desaturase Gene from Spinach in Transgenic Pigs","volume":"101","author":"Saeki","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/BF01969411","article-title":"Expression of Bacterial Cysteine Biosynthesis Genes in Transgenic Mice and Sheep: Toward a New in Vivo Amino Acid Biosynthesis Pathway and Improved Wool Growth","volume":"4","author":"Bawden","year":"1995","journal-title":"Transgenic Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/nbt783","article-title":"Cloned Transgenic Cattle Produce Milk with Higher Levels of Beta-Casein and Kappa-Casein","volume":"21","author":"Brophy","year":"2003","journal-title":"Nat. Biotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s11248-011-9554-2","article-title":"Production of Cloned Transgenic Cow Expressing Omega-3 Fatty Acids","volume":"21","author":"Wu","year":"2012","journal-title":"Transgenic Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0044-8486(98)00348-2","article-title":"Smolt Development in Growth Hormone Transgenic Atlantic Salmon1For the Department of Fisheries and Oceans, Government of Canada.1","volume":"168","author":"Saunders","year":"1998","journal-title":"Aquaculture"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3072","DOI":"10.2527\/1998.76123072x","article-title":"Production of Bovine \u03b1-Lactalbumin in the Milk of Transgenic Pigs1","volume":"76","author":"Bleck","year":"1998","journal-title":"J. Anim. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s11248-010-9409-2","article-title":"Production of Recombinant Human Lysozyme in the Milk of Transgenic Pigs","volume":"20","author":"Tong","year":"2011","journal-title":"Transgenic Res."},{"key":"ref_24","first-page":"313","article-title":"Transgenic Alteration of Sow Milk to Improve Piglet Growth and Health","volume":"58","author":"Wheeler","year":"2001","journal-title":"Reprod. Suppl."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1002\/mrd.21333","article-title":"Genetic Modifications of Pigs for Medicine and Agriculture","volume":"78","author":"Whyte","year":"2011","journal-title":"Mol. Reprod. Dev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1093\/biosci\/biv068","article-title":"Assessing Ecological and Evolutionary Consequences of Growth-Accelerated Genetically Engineered Fishes","volume":"65","author":"Devlin","year":"2015","journal-title":"Bioscience"},{"key":"ref_27","first-page":"544","article-title":"Genetic Engineering of Animals: Ethical Issues, Including Welfare Concerns","volume":"5","author":"Ormandy","year":"2011","journal-title":"Can. Vet. J."},{"key":"ref_28","unstructured":"Frewer, L. (2025, May 05). PEGASUS (Public Perception of Genetically Modified Animals\u2014Science, Utility and Society). Available online: https:\/\/cordis.europa.eu\/project\/id\/226465\/reporting."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Cunningham, F., Elliott, J., and Lees, P. (2010). Genetically Modified Animals and Pharmacological Research. Comparative and Veterinary Pharmacology, Springer.","DOI":"10.1007\/978-3-642-10324-7"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.tibtech.2019.12.015","article-title":"Options to Reform the European Union Legislation on GMOs: Post-Authorization and Beyond","volume":"38","author":"Eriksson","year":"2020","journal-title":"Trends Biotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e47812","DOI":"10.15252\/embr.201947812","article-title":"A Novel Governance Framework for GMO","volume":"20","author":"Bratlie","year":"2019","journal-title":"EMBO Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejor.2015.12.023","article-title":"Risk Assessment and Risk Management: Review of Recent Advances on Their Foundation","volume":"253","author":"Aven","year":"2016","journal-title":"Eur. J. Oper. Res."},{"key":"ref_33","first-page":"A104","article-title":"Outside Looking In: Understanding the Role of Science in Regulation","volume":"117","author":"Tim","year":"2009","journal-title":"Environ. Health Perspect."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Eckerstorfer, M.F., Engelhard, M., Heissenberger, A., Simon, S., and Teichmann, H. (2019). Plants Developed by New Genetic Modification Techniques-Comparison of Existing Regulatory Frameworks in the EU and Non-EU Countries. Front. Bioeng Biotechnol, 7.","DOI":"10.3389\/fbioe.2019.00026"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Mackenzie, R., Burhenne-Guilmin, F., La Vi\u00f1a, A.G.M., Werksman, J.D., Ascencio, A., Kinderlerer, J., Kummer, K., and Tapper, R. (2003). An Explanatory Guide to the Cartagena Protocol on Biosafety, IUCN.","DOI":"10.2305\/IUCN.CH.2003.EPLP.46.en"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Metje-Sprink, J., Menz, J., Modrzejewski, D., and Sprink, T. (2018). DNA-Free Genome Editing: Past, Present and Future. Front. Plant Sci., 9.","DOI":"10.3389\/fpls.2018.01957"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3647","DOI":"10.1093\/nar\/9.15.3647","article-title":"Oligonucleotide Directed Mutagenesis of the Human \u03b2-Globin Gene: A General Method for Producing Specific Point Mutations in Cloned DNA","volume":"9","author":"Schold","year":"1981","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/nrg2842","article-title":"Genome Editing with Engineered Zinc Finger Nucleases","volume":"11","author":"Urnov","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2174\/156652311794520111","article-title":"Meganucleases and Other Tools for Targeted Genome Engineering: Perspectives and Challenges for Gene Therapy","volume":"11","author":"Silva","year":"2011","journal-title":"Curr. Gene Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1002\/bit.24890","article-title":"Transcription Activator-like Effector Nucleases (TALENs): A Highly Efficient and Versatile Tool for Genome Editing","volume":"110","author":"Sun","year":"2013","journal-title":"Biotechnol. Bioeng."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1111\/tpj.13469","article-title":"From Classical Mutagenesis to Nuclease-Based Breeding\u2014Directing Natural DNA Repair for a Natural End-Product","volume":"90","author":"Pacher","year":"2017","journal-title":"Plant J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nbt.2142","article-title":"Deployment of New Biotechnologies in Plant Breeding","volume":"30","author":"Lusser","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.tibtech.2013.03.004","article-title":"Site-Directed Nucleases: A Paradigm Shift in Predictable, Knowledge-Based Plant Breeding","volume":"31","author":"Podevin","year":"2013","journal-title":"Trends Biotechnol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Holme, I.B., Gregersen, P.L., and Brinch-Pedersen, H. (2019). Induced Genetic Variation in Crop Plants by Random or Targeted Mutagenesis: Convergence and Differences. Front. Plant Sci., 10.","DOI":"10.3389\/fpls.2019.01468"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e2004831117","DOI":"10.1073\/pnas.2004831117","article-title":"CRISPR, Animals, and FDA Oversight: Building a Path to Success","volume":"118","author":"Epstein","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1126\/science.aad5227","article-title":"Rationally Engineered Cas9 Nucleases with Improved Specificity","volume":"351","author":"Slaymaker","year":"2016","journal-title":"Science"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/nature16526","article-title":"High-Fidelity CRISPR\u2013Cas9 Nucleases with No Detectable Genome-Wide off-Target Effects","volume":"529","author":"Kleinstiver","year":"2016","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nature24268","article-title":"Enhanced Proofreading Governs CRISPR\u2013Cas9 Targeting Accuracy","volume":"550","author":"Chen","year":"2017","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3048","DOI":"10.1038\/s41467-018-05477-x","article-title":"Directed Evolution of CRISPR-Cas9 to Increase Its Specificity","volume":"9","author":"Lee","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.cell.2015.09.038","article-title":"Cpf1 Is a Single RNA-Guided Endonuclease of a Class 2 CRISPR-Cas System","volume":"163","author":"Zetsche","year":"2015","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/nature24049","article-title":"RNA Targeting with CRISPR\u2013Cas13","volume":"550","author":"Abudayyeh","year":"2017","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1126\/science.aax9181","article-title":"RNA-Guided DNA Insertion with CRISPR-Associated Transposases","volume":"365","author":"Strecker","year":"2019","journal-title":"Science"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/s41586-019-1323-z","article-title":"Transposon-Encoded CRISPR\u2013Cas Systems Direct RNA-Guided DNA Integration","volume":"571","author":"Klompe","year":"2019","journal-title":"Nature"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"14500","DOI":"10.1038\/ncomms14500","article-title":"In Vivo Genome Editing with a Small Cas9 Orthologue Derived from Campylobacter Jejuni","volume":"8","author":"Kim","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"20969","DOI":"10.1073\/pnas.1906843116","article-title":"Rationally Engineered Staphylococcus Aureus Cas9 Nucleases with High Genome-Wide Specificity","volume":"116","author":"Tan","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/s41576-018-0059-1","article-title":"Base Editing: Precision Chemistry on the Genome and Transcriptome of Living Cells","volume":"19","author":"Rees","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.molcel.2017.09.029","article-title":"Methods and Applications of CRISPR-Mediated Base Editing in Eukaryotic Genomes","volume":"68","author":"Hess","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/s41586-019-1711-4","article-title":"Search-and-Replace Genome Editing without Double-Strand Breaks or Donor DNA","volume":"576","author":"Anzalone","year":"2019","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1111\/jipb.12734","article-title":"The CRISPR\/Cas Revolution Continues: From Efficient Gene Editing for Crop Breeding to Plant Synthetic Biology","volume":"60","author":"Kumlehn","year":"2018","journal-title":"J. Integr. Plant Biol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Sedeek, K.E.M., Mahas, A., and Mahfouz, M. (2019). Plant Genome Engineering for Targeted Improvement of Crop Traits. Front. Plant Sci., 10.","DOI":"10.3389\/fpls.2019.00114"},{"key":"ref_61","first-page":"117","article-title":"Following the Framework: Intentional Genomic Alterations in Animals","volume":"18","author":"Copper","year":"2023","journal-title":"J. Food Law. Policy"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/s41587-020-0413-7","article-title":"Genome Editing in Animals: Why FDA Regulation Matters","volume":"38","author":"Solomon","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_63","unstructured":"(2024, July 24). FDA\/CVM Heritable Intentional Genomic Alterations in Animals: Risk-Based Approach, Available online: https:\/\/www.fda.gov\/media\/74614\/download."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s11569-024-00455-8","article-title":"Gene Editing Cattle for Enhancing Heat Tolerance: A Welfare Review of the \u201cPRLR-SLICK Cattle\u201d Case","volume":"18","author":"Pozzebon","year":"2024","journal-title":"Nanoethics"},{"key":"ref_65","unstructured":"FDA\/CVM (2024, September 30). Heritable Intentional Genomic Alterations in Animals: The Approval Process Draft Guidance for Industry #187B, Available online: https:\/\/www.fda.gov\/media\/150658\/download."},{"key":"ref_66","unstructured":"EPA\/FDA\/USDA (2024, July 23). The Coordinated Framework for the Regulation of Biotechnology, Available online: https:\/\/www.epa.gov\/sites\/default\/files\/2017-01\/documents\/2017_coordinated_framework_update.pdf."},{"key":"ref_67","unstructured":"Lee, S.S. (2024, October 01). FDA\u2019s Regulation of Intentional Genomic Alterations in Animals Using Genome Editing, Available online: https:\/\/www.nist.gov\/system\/files\/documents\/2018\/05\/21\/5_stella_lee_cvm_april_2018.pdf."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1071\/EA03223","article-title":"Gene Transfer: Potential to Enhance the Genome of Atlantic Salmon for Aquaculture","volume":"44","author":"Fletcher","year":"2004","journal-title":"Aust. J. Exp. Agric."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.aquaculture.2013.05.005","article-title":"Effects of Combined \u2018All-Fish\u2019 Growth Hormone Transgenics and Triploidy on Growth and Nutrient Utilization of Atlantic Salmon (Salmo salar L.) Fed a Practical Grower Diet of Known Composition","volume":"406\u2013407","author":"Tibbetts","year":"2013","journal-title":"Aquaculture"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Clifford, H. (2014). AquAdvantage\u00ae Salmon\u2014A Pioneering Application of Biotechnology in Aquaculture. BMC Proc., 8.","DOI":"10.1186\/1753-6561-8-S4-O31"},{"key":"ref_71","unstructured":"FDA (2024, September 30). AquAdvantage Salmon Fact Sheet, Available online: https:\/\/www.fda.gov\/animal-veterinary\/aquadvantage-salmon\/aquadvantage-salmon-fact-sheet."},{"key":"ref_72","unstructured":"Walton, M., Beattie, C., and March, C. (2022, January 12\u201316). AquAdvantage Salmon: The Regulatory Journey. Proceedings of the 4th International Workshop\u2014Regulatory Approaches for Agricultural Applications of Animal Biotechnologies, S\u00e3o Paulo, Brazil."},{"key":"ref_73","unstructured":"Board of Directors of AquaBounty Technologies Inc (2025, May 05). AquaBounty Announces Plans to Cease Fish Farming Operations. Available online: https:\/\/investors.aquabounty.com\/news-releases\/news-release-details\/aquabounty-announces-plans-cease-fish-farming-operations."},{"key":"ref_74","unstructured":"FDA (2024, October 02). Freedom of Information Summary Original New Animal Drug Application NADA 141-454 OpAFP-GHc2 RDNA Construct in EO-1\u03b1 Lineage Atlantic Salmon (AquAdvantage Salmon), Available online: https:\/\/www.fda.gov\/files\/animal%20&%20veterinary\/published\/AquAdvantage-Salmon-FOI-Summary.pdf."},{"key":"ref_75","unstructured":"FDA\/CVM (2024, September 30). Appendix A to Aquabounty Salmon Approval, Available online: https:\/\/www.fda.gov\/media\/112646\/download."},{"key":"ref_76","unstructured":"AquaBounty Technologies Inc (2024, October 01). Environmental Assessment Supplement to NADA 141-454 to Allow the Grow-out of AquAdvantage Salmon at AquaBounty Technologies, Inc.\u2019s Indiana Facility, Available online: https:\/\/www.fda.gov\/media\/112655\/download."},{"key":"ref_77","unstructured":"FDA (2024, September 30). Finding of No Significant Impact (FONSI)\u2014AquAdvantage Salmon. Available online: https:\/\/aglaw.psu.edu\/wp-content\/uploads\/2020\/06\/AquAdvantage-Salmon-FONSI.pdf."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1095-8649.1995.tb06040.x","article-title":"Transgenic Salmon: Tailoring the Genome for Food Production","volume":"47","author":"Hew","year":"1995","journal-title":"J. Fish Biol."},{"key":"ref_79","unstructured":"FDA\/CVM (2024, September 30). Finding of No Significant Impact (FONSI)\u2014AquaBounty Technologies, Inc.\u2019s Indiana Facility, Available online: https:\/\/www.fda.gov\/media\/112663\/download."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s11248-006-0020-5","article-title":"Characterization and Multi-Generational Stability of the Growth Hormone Transgene (EO-1alpha) Responsible for Enhanced Growth Rates in Atlantic Salmon","volume":"15","author":"Yaskowiak","year":"2006","journal-title":"Transgenic Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1071\/RD07040","article-title":"Transgenic Farm Animals: An Update","volume":"19","author":"Niemann","year":"2007","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.theriogenology.2009.02.007","article-title":"Promoter Analysis of a Growth Hormone Transgene in Atlantic Salmon","volume":"72","author":"Butler","year":"2009","journal-title":"Theriogenology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.tibtech.2005.12.008","article-title":"Interface of Biotechnology and Ecology for Environmental Risk Assessments of Transgenic Fish","volume":"24","author":"Devlin","year":"2006","journal-title":"Trends Biotechnol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.aquaculture.2004.02.026","article-title":"Growth, Viability and Genetic Characteristics of GH Transgenic Coho Salmon Strains","volume":"236","author":"Devlin","year":"2004","journal-title":"Aquaculture"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/nbt0292-176","article-title":"Growth Enhancement in Transgenic Atlantic Salmon by the Use of an \u201cAll Fish\u201d Chimeric Growth Hormone Gene Construct","volume":"10","author":"Du","year":"1992","journal-title":"Nat. Biotechnol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/371209a0","article-title":"Extraordinary Salmon Growth","volume":"371","author":"Devlin","year":"1994","journal-title":"Nature"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.foodchem.2015.06.064","article-title":"A New Specific Reference Gene Based on Growth Hormone Gene (GH1) Used for Detection and Relative Quantification of Aquadvantage\u00ae GM Salmon (Salmo salar L.) in Food Products","volume":"190","author":"Nabi","year":"2016","journal-title":"Food Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1007\/s12161-018-1214-1","article-title":"Detection of Transgenic Atlantic and Coho Salmon by Real-Time PCR","volume":"11","author":"Debode","year":"2018","journal-title":"Food Anal. Methods"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.foodcont.2017.06.037","article-title":"A Method to Assemble DNA Fragments Mimicking Junctions of Transgenic Elements: Application to the AquAdvantage Salmon","volume":"82","author":"Castro","year":"2017","journal-title":"Food Control"},{"key":"ref_90","unstructured":"Godefroy, S. (2025, May 05). Codex Guidance on Assessment of Food Derived from Biotechnology. Available online: https:\/\/gforss.org\/wp-content\/uploads\/2024\/09\/1-2024_uaebiotechworkshop_FAOGMFSAssessment_vf.pdf."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Hayes, K.R., Kapuscinski, A.R., Dana, G., Li, S., and Devlin, R.H. (2007). Introduction to Environmental Risk Assessment for Transgenic Fish. CABI, 1\u201328.","DOI":"10.1079\/9781845932961.0001"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.aquaculture.2007.12.026","article-title":"Transgenic Approaches for the Reproductive Containment of Genetically Engineered Fish","volume":"275","author":"Wong","year":"2008","journal-title":"Aquaculture"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Devlin, R.H., and Donaldson, E.M. (1992). Containment of Genetically Altered Fish with Emphasis on Salmonids. Transgenic Fish, 229\u2013265.","DOI":"10.1142\/9789814503600_0013"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1111\/j.1467-2979.2010.00390.x","article-title":"Managing Non-Native Fish in the Environment","volume":"12","author":"Britton","year":"2011","journal-title":"Fish Fish."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"126604","DOI":"10.1016\/j.jclepro.2021.126604","article-title":"Recirculating Aquaculture Systems (RAS): Environmental Solution and Climate Change Adaptation","volume":"297","author":"Ahmed","year":"2021","journal-title":"J. Clean. Prod."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1139\/z73-135","article-title":"Ultimate Upper Lethal Temperature of Atlantic Salmon Salmo salar L.","volume":"51","author":"Garside","year":"1973","journal-title":"Can. J. Zool."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/j.1365-2427.1991.tb00473.x","article-title":"Tolerance and Resistance to Thermal Stress in Juvenile Atlantic Salmon, Salmo salar","volume":"25","author":"Elliott","year":"1991","journal-title":"Freshw. Biol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1139\/f89-097","article-title":"Temperature Requirements in Atlantic Salmon (Salmo salar), Brown trout (Salmo trutta), and Arctic Char (Salvelinus alpinus) from Hatching to Initial Feeding Compared with Geographic Distribution","volume":"46","author":"Jensen","year":"1989","journal-title":"Can. J. Fish. Aquat. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1046\/j.1365-2435.1997.00130.x","article-title":"A Functional Model for Maximum Growth of Atlantic Salmon Parr, Salmo salar, from Two Populations in Northwest England","volume":"11","author":"Elliott","year":"1997","journal-title":"Funct. Ecol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1007\/s10530-017-1384-6","article-title":"Towards the Genetic Control of Invasive Species","volume":"19","author":"Ant","year":"2017","journal-title":"Biol. Invasions"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Burnell, G., and Allan, G. (2009). 5\u2014Producing Sterile and Single-Sex Populations of Fish for Aquaculture. New Technologies in Aquaculture, Woodhead Publishing.","DOI":"10.1533\/9781845696474"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1111\/raq.12092","article-title":"Effectiveness of Triploidy as a Management Tool for Reproductive Containment of Farmed Fish: Atlantic Salmon (Salmo salar) as a Case Study","volume":"8","author":"Benfey","year":"2016","journal-title":"Rev. Aquac."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.aquaculture.2010.03.023","article-title":"Occurrence of Incomplete Paternal-Chromosome Retention in GH-Transgenic Coho Salmon Being Assessed for Reproductive Containment by Pressure-Shock-Induced Triploidy","volume":"304","author":"Devlin","year":"2010","journal-title":"Aquaculture"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.aquaculture.2010.11.044","article-title":"Cultured Growth Hormone Transgenic Salmon Are Reproductively Out-Competed by Wild-Reared Salmon in Semi-Natural Mating Arenas","volume":"312","author":"Fitzpatrick","year":"2011","journal-title":"Aquaculture"},{"key":"ref_105","first-page":"69E","article-title":"Defining Environmental Risk Assessment Criteria for Genetically Modified Fishes to Be Placed on the EU Market","volume":"7","author":"Cows","year":"2010","journal-title":"EFSA Support. Publ."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"EFSA Panel on Genetically Modified Organisms (GMO) (2013). Guidance on the Environmental Risk Assessment of Genetically Modified Animals. EFSA J., 11, 3200.","DOI":"10.2903\/j.efsa.2013.3200"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.nbt.2010.05.006","article-title":"The Costly Benefits of Opposing Agricultural Biotechnology","volume":"27","author":"Apel","year":"2010","journal-title":"New Biotechnol."},{"key":"ref_108","unstructured":"Funk, C. (2024, September 30). About Half of U.S. Adults Are Wary of Health Effects of Genetically Modified Foods, but Many Also See Advantages. Available online: https:\/\/www.pewresearch.org\/short-reads\/2020\/03\/18\/about-half-of-u-s-adults-are-wary-of-health-effects-of-genetically-modified-foods-but-many-also-see-advantages\/."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"104374","DOI":"10.1016\/j.foodqual.2021.104374","article-title":"Consumer Acceptance of Gene-Edited Food Products in China","volume":"95","author":"Ortega","year":"2022","journal-title":"Food Qual. Prefer."},{"key":"ref_110","first-page":"94","article-title":"Consumer Willingness to Pay for Genetically Modified Vegetable Oil and Salmon in the United States and Norway","volume":"20","author":"Rickertsen","year":"2017","journal-title":"AgBioForum"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Porto-Neto, L.R., Bickhart, D.M., Landaeta-Hernandez, A.J., Utsunomiya, Y.T., Pagan, M., Jimenez, E., Hansen, P.J., Dikmen, S., Schroeder, S.G., and Kim, E.S. (2018). Convergent Evolution of Slick Coat in Cattle through Truncation Mutations in the Prolactin Receptor. Front. Genet., 9.","DOI":"10.3389\/fgene.2018.00057"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/s41587-019-0394-6","article-title":"Template Plasmid Integration in Germline Genome-Edited Cattle","volume":"38","author":"Norris","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_113","unstructured":"FDA\/CVM (2024, September 30). Risk Assessment Summary-V-006378 PRLR-SLICK Cattle, Available online: https:\/\/www.fda.gov\/media\/155706\/download."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3395","DOI":"10.3168\/jds.2008-1072","article-title":"Differences in Thermoregulatory Ability between Slick-Haired and Wild-Type Lactating Holstein Cows in Response to Acute Heat Stress","volume":"91","author":"Dikmen","year":"2008","journal-title":"J. Dairy. Sci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"5508","DOI":"10.3168\/jds.2014-8087","article-title":"The SLICK Hair Locus Derived from Senepol Cattle Confers Thermotolerance to Intensively Managed Lactating Holstein Cows","volume":"97","author":"Dikmen","year":"2014","journal-title":"J. Dairy. Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"295","DOI":"10.2527\/1996.742295x","article-title":"Heat Tolerance in Two Tropically Adapted Bos Taurus Breeds, Senepol and Romosinuano, Compared with Brahman, Angus, and Hereford Cattle in Florida","volume":"74","author":"Hammond","year":"1996","journal-title":"J. Anim. Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.2527\/1998.7661568x","article-title":"Heat Tolerance in Tuli-, Senepol-, and Brahman-Sired F1 Angus Heifers in Florida","volume":"76","author":"Hammond","year":"1998","journal-title":"J. Anim. Sci."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"5861","DOI":"10.1038\/ncomms6861","article-title":"Functionally Reciprocal Mutations of the Prolactin Signalling Pathway Define Hairy and Slick Cattle","volume":"5","author":"Littlejohn","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"80","DOI":"10.2527\/2003.81180x","article-title":"Evidence of a Major Gene Influencing Hair Length and Heat Tolerance in Bos Taurus Cattle","volume":"81","author":"Olson","year":"2003","journal-title":"J. Anim. Sci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"42539","DOI":"10.1007\/s11356-022-19718-6","article-title":"A Review of the Global Climate Change Impacts, Adaptation, and Sustainable Mitigation Measures","volume":"29","author":"Abbass","year":"2022","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/age.13027","article-title":"Three Novel Nonsense Mutations of Prolactin Receptor Found in Heat-Tolerant Bos Taurus Breeds of the Caribbean Basin","volume":"52","author":"Kim","year":"2021","journal-title":"Anim. Genet."},{"key":"ref_122","unstructured":"(2022). CRISPR Beef Cattle Get FDA Green Light. Nat. Biotechnol., 40."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1007\/s10545-012-9475-0","article-title":"Genetically Modified Pigs for Biomedical Research","volume":"35","author":"Luo","year":"2012","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_124","unstructured":"FDA\/CVM (2025, May 15). Freedom of Information Summary Original New Drug Application NADA 141-542 PPL657 rDNA Construct in Domestic Pigs, Available online: https:\/\/www.federalregister.gov\/documents\/2021\/04\/01\/2021-06704\/new-animal-drugs-approval-of-new-animal-drug-applications."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Hawthorne, W.J. (2024). Ethical and Legislative Advances in Xenotransplantation for Clinical Translation: Focusing on Cardiac, Kidney and Islet Cell Xenotransplantation. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1355609"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1152\/physrev.00041.2023","article-title":"Physiological Basis for Xenotransplantation from Genetically-Modified Pigs to Humans: A Review","volume":"104","author":"Peterson","year":"2024","journal-title":"Physiol. Rev."},{"key":"ref_127","unstructured":"Farm Journal\u2019s Pork (2025, May 15). FDA Approves First-of-Its-Kind Intentional Genomic Alteration in Line of Domestic Pigs for Both Human Food, Potential Therapeutic Uses. Available online: https:\/\/www.porkbusiness.com\/news\/industry\/fda-approves-first-its-kind-intentional-genomic-alteration-pigs."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"e411","DOI":"10.1016\/j.jtcvs.2021.03.100","article-title":"Allergic Response to Medical Products in Patients with Alpha-Gal Syndrome","volume":"164","author":"Kuravi","year":"2022","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.athoracsur.2021.05.025","article-title":"The Genetically Engineered Heart as a Bridge to Allotransplantation in Infants Just Around the Corner?","volume":"114","author":"Cleveland","year":"2022","journal-title":"Ann. Thorac. Surg."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Goerlich, C.E., DiChiacchio, L., Zhang, T., Singh, A.K., Lewis, B., Tatarov, I., Hershfeld, A., Sentz, F., Ayares, D., and Corcoran, P. (2020). Heterotopic Porcine Cardiac Xenotransplantation in the Intra-Abdominal Position in a Non-Human Primate Model. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-66430-x"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.1038\/s41467-024-47679-6","article-title":"Consistent Survival in Consecutive Cases of Life-Supporting Porcine Kidney Xenotransplantation Using 10GE Source Pigs","volume":"15","author":"Eisenson","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1093\/ndt\/gfz174","article-title":"A Single Number for Advocacy and Communication-Worldwide More than 850 Million Individuals Have Kidney Diseases","volume":"34","author":"Jager","year":"2019","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0140-6736(20)30045-3","article-title":"Global, Regional, and National Burden of Chronic Kidney Disease, 1990\u20132017: A Systematic Analysis for the Global Burden of Disease Study 2017","volume":"395","author":"Bikbov","year":"2020","journal-title":"Lancet"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.kint.2024.01.016","article-title":"Physiologic Homeostasis after Pig-to-Human Kidney Xenotransplantation","volume":"105","author":"Judd","year":"2024","journal-title":"Kidney Int."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1056\/NEJMoa2120238","article-title":"Results of Two Cases of Pig-to-Human Kidney Xenotransplantation","volume":"386","author":"Montgomery","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1001\/jamasurg.2023.2774","article-title":"Normal Graft Function After Pig-to-Human Kidney Xenotransplant","volume":"158","author":"Locke","year":"2023","journal-title":"JAMA Surg."},{"key":"ref_137","unstructured":"Revivicor GalSafe\u00ae (2024, July 19). Pigs Environmental Assessment, Available online: https:\/\/animaldrugsatfda.fda.gov\/adafda\/app\/search\/public\/document\/downloadEA\/2962."},{"key":"ref_138","unstructured":"FDA\/CVM (2024, July 19). Finding of No Significant Impact (FONSI) in Support of an Approval of a New Animal Drug Application NADA 141-542 PPL657 rDNA Construct in the Glycoprotein Galactosyltransferase Alpha 1,3 Gene (GGTA1) in the Hemizygous and Homozygous GalSafe\u00ae Lineage of Domestic Pigs (Sus Scrofa Domesticus), Available online: https:\/\/public-inspection.federalregister.gov\/2021-06704.pdf?1617194732."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/35024082","article-title":"Cloned Pigs Produced by Nuclear Transfer from Adult Somatic Cells","volume":"407","author":"Polejaeva","year":"2000","journal-title":"Nature"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1126\/science.1078942","article-title":"Production of Alpha 1,3-Galactosyltransferase-Deficient Pigs","volume":"299","author":"Phelps","year":"2003","journal-title":"Science"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1111\/ajt.16930","article-title":"First Clinical-Grade Porcine Kidney Xenotransplant Using a Human Decedent Model","volume":"22","author":"Porrett","year":"2022","journal-title":"Am. J. Transplant."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1056\/NEJMoa2201422","article-title":"Genetically Modified Porcine-to-Human Cardiac Xenotransplantation","volume":"387","author":"Griffith","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1007\/s11248-008-9206-3","article-title":"Animal Pharming, Two Decades On","volume":"17","author":"Kind","year":"2008","journal-title":"Transgenic Res."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/S0167-7799(03)00190-2","article-title":"Making Recombinant Proteins in Animals\u2014Different Systems, Different Applications","volume":"21","author":"Dyck","year":"2003","journal-title":"Trends Biotechnol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.cimid.2007.11.005","article-title":"Production of Pharmaceutical Proteins by Transgenic Animals","volume":"32","author":"Houdebine","year":"2009","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"ref_146","unstructured":"FDA\/CVM (2024, July 19). Freedom of Information Summary Original New Animal Drug Application NADA 141-511 Bc2371 rDNA Construct in R69 New Zealand White Rabbits Heritable Construct Domesticated Rabbits, Available online: https:\/\/www.fda.gov\/animal-veterinary\/biotechnology-products-cvm-animals-and-animal-food\/intentional-genomic-alterations-igas-animals."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"518","DOI":"10.2146\/news090023","article-title":"FDA Approves First Biological Product Derived from Transgenic Animal","volume":"66","author":"Lavine","year":"2009","journal-title":"Am. J. Health-Syst. Pharm."},{"key":"ref_148","unstructured":"FDA\/CVM (2024, July 19). Freedom of Information Summary Original New Animal Drug Application NADA 141-294 Bc6 rDNA Construct in GTC 155-92 Goats, Available online: https:\/\/www.federalregister.gov\/documents\/2009\/02\/11\/E9-2881\/new-animal-drugs-bc6-recombinant-deoxyribonucleic-acid-construct."},{"key":"ref_149","unstructured":"FDA\/CVM (2024, July 19). Freedom of Information Summary Original New Animal Drug Application NADA 141-453 HLAL rDNA Construct in SBC LAL-C Chickens Heritable Construct Domesticated Chickens, Available online: https:\/\/dailymed.nlm.nih.gov\/dailymed\/fda\/fdaDrugXsl.cfm?setid=cc36144d-c62f-432d-bdac-10c0366a0866."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/s41684-019-0392-9","article-title":"A Multi-Animal Model Collaboration to Speed up Rare Disease Research","volume":"48","author":"Doughman","year":"2019","journal-title":"Lab Anim."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Berube, D.M. (2023). Oxitec. Pandemics and Resilience: Lessons We Should Have Learned from Zika, Springer International Publishing.","DOI":"10.1007\/978-3-031-25370-6"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.meegid.2018.11.009","article-title":"Aedes aegypti Vector Competence Studies: A Review","volume":"67","author":"Powell","year":"2019","journal-title":"Infect. Genet. Evol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1038\/s41467-020-16010-4","article-title":"Accelerating Invasion Potential of Disease Vector Aedes aegypti under Climate Change","volume":"11","author":"Iwamura","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_154","first-page":"120","article-title":"Similar Vertical Transmission Rates of Dengue and Chikungunya Viruses in a Transgenic and a Non-Transformed Aedes aegypti (L.) Laboratory Strain","volume":"33","author":"Ummu","year":"2016","journal-title":"Trop. Biomed."},{"key":"ref_155","unstructured":"Glandorf, D.C.M. (2024, October 01). Technical Evaluation of a Potential Release of OX513A Aedes aegypti Mosquitoes on the Island of Saba. Available online: https:\/\/www.rivm.nl\/bibliotheek\/rapporten\/2017-0087.pdf."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Hendrichs, J., Pereira, R., and Vreysen, M.J.B. (2021). Area-Wide Integrated Pest Management: Development and Field Application, CRC Press. [1st ed.].","DOI":"10.1201\/9781003169239"},{"key":"ref_157","unstructured":"HHS\/FDA\/CVM (2024, July 19). Environmental Assessment for Investigational Use of Aedes aegypti OX513A, Available online: https:\/\/www.fda.gov\/downloads\/AnimalVeterinary\/DevelopmentApprovalProcess\/GeneticEngineering\/GeneticallyEngineeredAnimals\/UCM514698.pdf."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s10669-018-9688-3","article-title":"A \u201cSolution-Focused\u201d Comparative Risk Assessment of Conventional and Synthetic Biology Approaches to Control Mosquitoes Carrying the Dengue Fever Virus","volume":"38","author":"Finkel","year":"2018","journal-title":"Environ. Syst. Decis."},{"key":"ref_159","unstructured":"HHS\/FDA\/CVM (2024, July 20). Finding of No Significant Impact (FONSI) in Support of a Proposed Field Trial of Genetically Engineered (GE) Male Aedes aegypti Mosquitoes of the Line OX513A in Key Haven, Monroe County, Florida under an Investigational New Animal Drug Exemption, Available online: https:\/\/www.fda.gov\/media\/133802\/download."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Bryk, J., Reeves, R.G., Reed, F.A., and Denton, J.A. (2017). Transcriptional Effects of a Positive Feedback Circuit in Drosophila Melanogaster. BMC Genom., 18.","DOI":"10.1186\/s12864-017-4385-z"},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Bourtzis, K., and Vreysen, M.J.B. (2021). Sterile Insect Technique (SIT) and Its Applications. Insects, 12.","DOI":"10.3390\/insects12070638"},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Marec, F., and Vreysen, M.J.B. (2019). Advances and Challenges of Using the Sterile Insect Technique for the Management of Pest Lepidoptera. Insects, 10.","DOI":"10.3390\/insects10110371"},{"key":"ref_163","unstructured":"HHS\/FDA\/CVM (2024, September 30). Guidance for Industry #236 Clarification of FDA and EPA Jurisdiction Over Mosquito-Related Products, Available online: https:\/\/www.fda.gov\/media\/102158\/download."},{"key":"ref_164","unstructured":"(2022). Japan Embraces CRISPR-Edited Fish. Nat. Biotechnol., 40."},{"key":"ref_165","unstructured":"Dionglay, C. (2025, April 04). Japan\u2019s Three Genome-Edited Food Products Reach Consumers. Available online: https:\/\/www.isaaa.org\/blog\/entry\/default.asp?BlogDate=1\/19\/2022."},{"key":"ref_166","unstructured":"Marsden, H. (2025, March 10). In Global First, Argentina Gallops Ahead of Other Western Countries in Producing CRISPR Horses and Other Animals. Available online: https:\/\/geneticliteracyproject.org\/2025\/02\/12\/in-global-first-argentina-gallops-ahead-of-other-western-countries-in-producing-crispr-horses-and-other-animals\/."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.tibtech.2014.03.005","article-title":"Caution Required for Handling Genome Editing Technology","volume":"32","author":"Araki","year":"2014","journal-title":"Trends Biotechnol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"5908","DOI":"10.1021\/es0704129","article-title":"An In Vivo Multiwell-Based Fluorescent Screen for Monitoring Vertebrate Thyroid Hormone Disruption","volume":"41","author":"Fini","year":"2007","journal-title":"Environ. Sci. Technol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"7525","DOI":"10.1021\/es202248h","article-title":"Zebrafish Eleutheroembryos Provide a Suitable Vertebrate Model for Screening Chemicals That Impair Thyroid Hormone Synthesis","volume":"45","author":"Thienpont","year":"2011","journal-title":"Environ. Sci. Technol."},{"key":"ref_170","unstructured":"Swett Walker, M. (2025, March 11). Meet Watchfrogs: GM Frogs and Fish Detect Endocrine Disrupting Chemicals in Wastewater. Available online: https:\/\/geneticliteracyproject.org\/2015\/06\/11\/meet-watchfrogs-gm-frogs-and-fish-detect-endocrine-disrupting-chemicals-in-wastewater\/."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s11248-017-0049-7","article-title":"Genome Editing in Livestock: Are We Ready for a Revolution in Animal Breeding Industry?","volume":"26","author":"Ruan","year":"2017","journal-title":"Transgenic Res."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s00003-014-0898-4","article-title":"EFSA Guidelines on the Environmental Risk Assessment of Genetically Modified Animals in the EU: The Process and Risk Assessment Considerations","volume":"9","author":"Mestdagh","year":"2014","journal-title":"J. Verbraucherschutz Leb."},{"key":"ref_173","first-page":"8311E","article-title":"New Genomic Techniques (NGT) in Animals and Their Agri\/Food\/Feed Products","volume":"20","year":"2023","journal-title":"EFSA Support. Public"},{"key":"ref_174","unstructured":"EFSA (2025, May 07). Genetically Modified Organisms. Available online: https:\/\/www.efsa.europa.eu\/en\/topics\/genetically-modified-organisms#latest."},{"key":"ref_175","unstructured":"EFSA (2025, May 07). Genetically Modified Animals. Available online: https:\/\/www.efsa.europa.eu\/en\/topics\/topic\/genetically-modified-animals."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"EFSA Panels on Genetically Modified Organisms (GMO), and Animal Health and Welfare (AHAW) (2012). Guidance on the Risk Assessment of Food and Feed from Genetically Modified Animals and on Animal Health and Welfare Aspects. EFSA J., 10, 2501.","DOI":"10.2903\/j.efsa.2012.2501"},{"key":"ref_177","unstructured":"ISAAA (2025, March 10). Spineless Fish Developed Through Genome Editing in China. Available online: https:\/\/www.isaaa.org\/kc\/cropbiotechupdate\/ged\/article\/default.asp?ID=19352."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1126\/science.365.6452.420","article-title":"China\u2019s CRISPR Revolution","volume":"365","author":"Cohen","year":"2019","journal-title":"Science"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/s41587-019-0138-7","article-title":"Worldwide CRISPR Patent Landscape Shows Strong Geographical Biases","volume":"37","author":"Kuntz","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_180","unstructured":"Cohen, J. (2025, March 22). To Feed Its 1.4 Billion, China Bets Big on Genome Editing of Crops. Available online: https:\/\/www.science.org\/content\/article\/feed-its-14-billion-china-bets-big-genome-editing-crops."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s43016-020-0051-8","article-title":"A CRISPR Way for Accelerating Improvement of Food Crops","volume":"1","author":"Zhang","year":"2020","journal-title":"Nat. Food"},{"key":"ref_182","unstructured":"Ventura, L. (2025, March 12). As the CRISPR Revolution Advances, Here\u2019s How Gene Editing Will Actually Help Farmers and Consumers. Available online: https:\/\/geneticliteracyproject.org\/2020\/12\/15\/as-the-crispr-revolution-proceeds-heres-how-gene-editing-will-actually-help-farmers-and-consumers\/."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/15\/11\/1570\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:41:46Z","timestamp":1760031706000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/15\/11\/1570"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,27]]},"references-count":182,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ani15111570"],"URL":"https:\/\/doi.org\/10.3390\/ani15111570","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,27]]}}}