{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T06:23:37Z","timestamp":1792218217948,"version":"4.4.0"},"reference-count":19,"publisher":"SAGE Publications","issue":"17-18","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:p>Gene therapy has revolutionized modern medicine by offering innovative treatments for genetic disorders, cancers, and immune-related conditions through technologies such as viral vector delivery, genome editing, and genetically modified cell therapies. Despite significant advancements, the classification of gene therapy medicinal products (GTMPs) as genetically modified organisms (GMOs) under EU legislation imposes significant regulatory burdens, hindering early and timely patient access to such therapies. Current GMO regulations, originally designed for agricultural biotechnology, require environmental risk assessments (ERAs) and additional approvals, creating delays and increasing costs\u2014with a particularly negative impact on early academic research. This article examines the scientific and regulatory discrepancies in classifying GTMPs as GMOs, arguing that replication-deficient vectors and non-persistent modified cells may not meet the criteria for GMOs. We highlight the negative impact of GMO requirements on clinical trial feasibility in Europe compared to the U.S., where a categorical exclusion from ERA applies to investigational medicinal products. Proposed solutions include adopting a risk-based regulatory model, harmonizing ERA processes under the revised EU Clinical Trials Regulation, and establishing exemptions for low-risk therapies. By aligning regulatory frameworks with scientific evidence, policymakers can accelerate the translation of gene therapies while maintaining safety standards, ultimately improving patient access to these transformative treatments.<\/jats:p>","DOI":"10.1177\/10430342251372063","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T17:58:13Z","timestamp":1757959093000},"page":"1154-1158","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Regulatory Strategies for Accelerating the Translation of Gene Therapies to Clinical Practice: Focus on GMO Considerations"],"prefix":"10.1177","volume":"36","author":[{"given":"Joaquin","family":"Delgadillo","sequence":"first","affiliation":[{"name":"Banc de Sang i Teixits (BST), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1961-8612","authenticated-orcid":false,"given":"Francisco","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), Granada, Spain"},{"name":"Department of Biochemistry and Molecular Biology III and Immunology, Faculty of Medicine, University of Granada, Granada, Spain"},{"name":"Biosanitary Research Institute of Granada (IBS.GRANADA), University of Granada, Granada, Spain"},{"name":"Excellence Research Unit \u201cModeling Nature\u201d (MNat), University of Granada, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Carmona","sequence":"additional","affiliation":[{"name":"Red Andaluza de dise\u00f1o y traslaci\u00f3n de Terapias Avanzadas-RAdytTA, Fundaci\u00f3n P\u00fablica Andaluza Progreso y Salud-FPS, Sevilla, Espa\u00f1a"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep M.","family":"Canals","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells and Regenerative Medicine, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain"},{"name":"Creatio, Production and Validation Center of Advanced Therapies, University of Barcelona, Barcelona, Spain"},{"name":"Institute of Neurosciences, University of Barcelona, Barcelona, Spain"},{"name":"August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Rio","sequence":"additional","affiliation":[{"name":"Division of Hematopoietic Innovative Therapies, Centro de Investigaciones Energ\u00e9ticas Medioambientales y Tecnol\u00f3gicas and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIEMAT\/CIBERER), Madrid, Spain"},{"name":"Advanced Therapies Unit, Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS-FJD, UAM), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Eguizabal","sequence":"additional","affiliation":[{"name":"Advanced Therapies Unit, Osakidetza, Basque Centre for Blood Transfusion and Human Tissues, Galdakao, Spain"},{"name":"Cell Therapy, Stem Cells and Tissues Group, Biobizkaia Health Research Institute, Barakaldo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Prosper","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda y Terapia Celular, Cl\u00ednica Universidad de Navarra (CUN), Cancer Centre Cl\u00ednica Universidad de Navarra (CCUN), Pamplona, Spain"},{"name":"CIBERONC, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Avenda\u00f1o-Sol\u00e1","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"e_1_3_3_2_2","unstructured":"Official Journal of the European Communities. (2001). Directive 2001\/18\/EC of the European Parliament and of the Council of 12 March 2001 on the Deliberate Release into the Environment of Genetically Modified Organisms and Repealing Council Directive 90\/220\/EEC. Available from: https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/PDF\/?uri=OJ:L:2001:106:FULL&from=EN [Last accessed: June30 2025]."},{"key":"e_1_3_3_3_2","unstructured":"Official Journal of the European Union. (2009). Directive 2009\/41\/EC of the European Parliament and of the Council of 6 May 2009 on the Contained Use of Genetically Modified Micro-organisms (Recast). Available from: https:\/\/eur-lex.europa.eu\/LexUriServ\/LexUriServ.do?uri=OJ:L:2009:125:0075:0097:EN:PDF [Last accessed: June30 2025]."},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1089\/humc.2019.042"},{"key":"e_1_3_3_5_2","unstructured":"European Commission. Genetically Modified Organism (GMO) Aspects for Investigational Medicinal Products. Available from: https:\/\/health.ec.europa.eu\/medicinal-products\/advanced-therapies\/genetically-modified-organism-gmo-aspects-investigational-medicinal-products_en#latest-updates"},{"key":"e_1_3_3_6_2","unstructured":"Case C-528\/16 Judgement of the Court (Grande Chambre) of 25 July 2018. Available from: https:\/\/eur-lex.europa.eu\/legal-content\/ES\/TXT\/PDF\/?uri=CELEX:62016CJ0528 [Last accessed: June30 2025]."},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/10408444.2019.1689380"},{"key":"e_1_3_3_8_2","unstructured":"US Food and Drug Administration. Code of Federal Regulations Title 21 Part 25. Environmental Impact Considerations. Subpart C\u2014Categorical Exclusions. Sec. 25.31. Available from: https:\/\/www.ecfr.gov\/current\/title-21\/chapter-I\/subchapter-A\/part-25\/subpart-C\/section-25.31 [Last accessed: June30 2025]."},{"key":"e_1_3_3_9_2","unstructured":"European Commission DG Health and Food Safety and European Medicines Agency Action Plan on ATMPs. Available from: www.ema.europa.eu\/en\/documents\/other\/european-commission-dg-health-and-food-safety-and-european-medicines-agency-action-plan-advanced-therapy-medicinal-products-atmps_en.pdf [Last accessed: June30 2025]."},{"key":"e_1_3_3_10_2","unstructured":"Common application form for viral vectors contained in investigational medicinal products for human use. Available from: https:\/\/ec.europa.eu\/health\/sites\/health\/files\/files\/advtherapies\/docs\/vvs_caf_en.pdf"},{"key":"e_1_3_3_11_2","unstructured":"Common application form for investigational medicinal products for human use that contain or consist of AAV vectors. Available from: https:\/\/ec.europa.eu\/health\/sites\/health\/files\/files\/advtherapies\/docs\/aavs_caf_en.pdf [Last accessed: June30 2025]."},{"key":"e_1_3_3_12_2","unstructured":"Common Application form for clinical research with human cells genetically modified by means of retro\/lentiviral vectors. Available from: https:\/\/ec.europa.eu\/health\/sites\/health\/files\/files\/advtherapies\/docs\/gmcells_caf_en.pdf [Last accessed: June30 2025]."},{"key":"e_1_3_3_13_2","unstructured":"Good Practice on the assessment of GMO related aspects in the context of clinical trials with AAV clinical vectors. Available from: https:\/\/ec.europa.eu\/health\/sites\/health\/files\/files\/advtherapies\/docs\/aavs_gp_en.pdf [Last accessed: June30 2025]."},{"key":"e_1_3_3_14_2","unstructured":"Good Practice on the assessment of GMO-related aspects in the context of clinical trials with human cells genetically modified by means of retro\/lentiviral vectors. Available from: https:\/\/ec.europa.eu\/health\/sites\/health\/files\/files\/advtherapies\/docs\/gmcells_gp_en.pdf [Last accessed: June30 2025]."},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2021.058"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13795"},{"key":"e_1_3_3_17_2","unstructured":"European Commission. Proposal for a Regulation laying down Union procedures for the authorisation and supervision of medicinal products for human use and establishing rules governing the European Medicines Agency. April 2023. Available from: https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/?uri=CELEX:52023PC0193"},{"key":"e_1_3_3_18_2","unstructured":"European Commission. Proposal for a Directive on the Union code relating to medicinal products for human use. April 2023. Available from: https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/?uri=CELEX:52023PC0192"},{"key":"e_1_3_3_19_2","unstructured":"EFPIA. Improving EU Clinical Trials: Proposals to Overcome Current Challenges and Strengthen the Ecosystem. 15 April 2025. Available from: www.efpia.eu\/media\/pl0nag0s\/efpias-list-of-proposals-clinical-trials-15-apr-2025.pdf [Last accessed: August3 2025]."},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-023-07869-x"}],"container-title":["Human Gene Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/10430342251372063","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10430342251372063","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10430342251372063","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:50:45Z","timestamp":1777449045000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/10430342251372063"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,21]]},"references-count":19,"journal-issue":{"issue":"17-18","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1177\/10430342251372063"],"URL":"https:\/\/doi.org\/10.1177\/10430342251372063","relation":{},"ISSN":["1043-0342","1557-7422"],"issn-type":[{"value":"1043-0342","type":"print"},{"value":"1557-7422","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,21]]}}}