{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T22:01:14Z","timestamp":1783116074388,"version":"3.54.6"},"reference-count":397,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["23-64-00002"],"award-info":[{"award-number":["23-64-00002"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["075-03-2023-106\/12"],"award-info":[{"award-number":["075-03-2023-106\/12"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The liver is a primary metabolic hub and a pivotal target for gene therapy, owing to its capacity for protein secretion, role in metabolic homeostasis and immune tolerance. Liver-directed gene therapies are used to treat numerous inherited metabolic disorders and coagulation factor deficiencies including hemophilia (A and B), Crigler\u2013Najjar syndrome, mucopolysaccharidoses, phenylketonuria, Fabry, Gaucher, Wilson and Pompe diseases. The efficacy and safety of liver-directed gene therapy rely on the use of strong tissue-specific promoters. To date, there are many different liver-specific promoters used in preclinical and clinical studies, including novel completely synthetic promoters. This review provides a comprehensive analysis of the design, engineering and application of liver-specific promoters. Furthermore, we discuss fundamental principles of gene expression regulation in the liver and the physiological and immunological characteristics that make it a suitable target organ for gene therapy delivery.<\/jats:p>","DOI":"10.3390\/cells15010014","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T07:01:33Z","timestamp":1766386893000},"page":"14","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Engineering Liver-Specific Promoters: A Comprehensive Review of Design, Mechanisms, and Clinical Applications in Gene Therapy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1774-6656","authenticated-orcid":false,"given":"Valentin","family":"Artemyev","sequence":"first","affiliation":[{"name":"Moscow Center for Advanced Studies, Kulakova Str. 20, Moscow 123592, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0986-686X","authenticated-orcid":false,"given":"Anastasiia Iu.","family":"Paremskaia","sequence":"additional","affiliation":[{"name":"Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, Moscow 125315, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7239-8474","authenticated-orcid":false,"given":"Amina A.","family":"Dzhioeva","sequence":"additional","affiliation":[{"name":"Moscow Center for Advanced Studies, Kulakova Str. 20, Moscow 123592, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7188-6956","authenticated-orcid":false,"given":"Daria","family":"Mishina","sequence":"additional","affiliation":[{"name":"Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, Moscow 125315, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6377-9056","authenticated-orcid":false,"given":"Viktor","family":"Bogdanov","sequence":"additional","affiliation":[{"name":"Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, Moscow 125315, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7963-5022","authenticated-orcid":false,"given":"Julia","family":"Krupinova","sequence":"additional","affiliation":[{"name":"Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, Moscow 125315, Russia"},{"name":"Moscow Clinical Scientific Center N.A. 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Loginov, Moscow 111123, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5982-8393","authenticated-orcid":false,"given":"Ali","family":"Mazloum","sequence":"additional","affiliation":[{"name":"Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, Moscow 125315, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7608-439X","authenticated-orcid":false,"given":"Sofya G.","family":"Feoktistova","sequence":"additional","affiliation":[{"name":"Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, Moscow 125315, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9252-1601","authenticated-orcid":false,"given":"Olga N.","family":"Mityaeva","sequence":"additional","affiliation":[{"name":"Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, Moscow 125315, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9794-6297","authenticated-orcid":false,"given":"Pavel Yu.","family":"Volchkov","sequence":"additional","affiliation":[{"name":"Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, Moscow 125315, Russia"},{"name":"Moscow Clinical Scientific Center N.A. A.S. Loginov, Moscow 111123, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.3390\/ph5121372","article-title":"The Liver as a Target Organ for Gene Therapy: State of the Art, Challenges, and Future Perspectives","volume":"5","author":"Jacobs","year":"2012","journal-title":"Pharmaceuticals"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1136\/adc.2005.091637","article-title":"The Incidence of Inherited Metabolic Disorders in the West Midlands, UK","volume":"91","author":"Sanderson","year":"2006","journal-title":"Arch. Dis. Child."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/jimd.12637","article-title":"Liver Directed Adeno-associated Viral Vectors to Treat Metabolic Disease","volume":"47","author":"Chuecos","year":"2024","journal-title":"J. Inherit. Metab. 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