{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:39:38Z","timestamp":1787791178003,"version":"build-2784847793"},"reference-count":107,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T00:00:00Z","timestamp":1768003200000},"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":["24-25-00203"],"award-info":[{"award-number":["24-25-00203"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute Respiratory Distress Syndrome (ARDS) is a severe complication of acute lung injury (ALI) characterized by acute hypoxemic respiratory failure and diffuse alveolar damage, with a high mortality rate and a current lack of treatments beyond supportive care. Its complex pathophysiology involves immune cell activation, pro-inflammatory cytokine release, and disruption of the alveolar\u2013capillary barrier, leading to pulmonary edema and fibrosis. This review explores the potential of small interfering RNA (siRNA) therapy as a novel pathogenetic treatment for ARDS. The mechanism of RNA interference is described, highlighting its high specificity for silencing target genes. The paper then evaluates various animal models used in ARDS preclinical research, noting the advantages of large animals (pigs) for their physiological similarity to humans and the suitability of rodents for studying long-term fibrotic stages. Finally, the review summarizes promising in vivo studies where siRNA-mediated knockdown of several genes (e.g., TIMP1, BTK, LCN2, HDAC7, CCL2, NOX4, TNF\u03b1 and TLR4) significantly reduced inflammation, improved lung histology, and increased survival. The collective evidence underscores siRNA\u2019s considerable potential for developing targeted therapies against ARDS, moving beyond symptomatic care to address the root molecular mechanisms of the disease.<\/jats:p>","DOI":"10.3390\/ijms27020717","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T09:13:01Z","timestamp":1768209181000},"page":"717","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Small Interfering RNA (siRNA) as a Targeted Therapy for Acute Respiratory Distress Syndrome: Evidence from Experimental Models"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3001-4820","authenticated-orcid":false,"given":"Viktoriia","family":"Kiseleva","sequence":"first","affiliation":[{"name":"National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation, 117198 Moscow, Russia"},{"name":"Research Institute of Molecular and Cellular Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8650-8240","authenticated-orcid":false,"given":"Polina","family":"Vishnyakova","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation, 117198 Moscow, Russia"},{"name":"Research Institute of Molecular and Cellular Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2392-4439","authenticated-orcid":false,"given":"Andrey","family":"Elchaninov","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation, 117198 Moscow, Russia"},{"name":"Research Institute of Molecular and Cellular Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 117198 Moscow, Russia"},{"name":"Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution \u201cPetrovsky National Research Centre of Surgery\u201d, 117418 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3366-4113","authenticated-orcid":false,"given":"Ivan","family":"Kiselev","sequence":"additional","affiliation":[{"name":"Chazov National Medical Research Center of Cardiology, Ministry of Health of the Russian Federation, 121552 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennady","family":"Sukhikh","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. 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Kulakov of Ministry of Healthcare of Russian Federation, 117198 Moscow, Russia"},{"name":"Research Institute of Molecular and Cellular Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 117198 Moscow, Russia"},{"name":"Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution \u201cPetrovsky National Research Centre of Surgery\u201d, 117418 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,10]]},"reference":[{"key":"ref_1","unstructured":"Diamond, M., Peniston, H.L., Sanghavi, D.K., and Mahapatra, S. (2025). 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