{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T20:55:58Z","timestamp":1789505758817,"version":"build-2803163510"},"reference-count":310,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T00:00:00Z","timestamp":1645488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1128012"],"award-info":[{"award-number":["1128012"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1149990"],"award-info":[{"award-number":["APP1149990"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1173363"],"award-info":[{"award-number":["APP1173363"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["2011467"],"award-info":[{"award-number":["2011467"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1175134"],"award-info":[{"award-number":["1175134"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Since December 2019, a pandemic of COVID-19 disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread across the globe. At present, the Food and Drug Administration (FDA) has issued emergency approval for the use of some antiviral drugs. However, these drugs still have limitations in the specific treatment of COVID-19, and as such, new treatment strategies urgently need to be developed. RNA-interference-based gene therapy provides a tractable target for antiviral treatment. Ensuring cell-specific targeted delivery is important to the success of gene therapy. The use of nanoparticles (NPs) as carriers for the delivery of small interfering RNA (siRNAs) to specific tissues or organs of the human body could play a crucial role in the specific therapy of severe respiratory infections, such as COVID-19. In this review, we describe a variety of novel nanocarriers, such as lipid NPs, star polymer NPs, and glycogen NPs, and summarize the pre-clinical\/clinical progress of these nanoparticle platforms in siRNA delivery. We also discuss the application of various NP-capsulated siRNA as therapeutics for SARS-CoV-2 infection, the challenges with targeting these therapeutics to local delivery in the lung, and various inhalation devices used for therapeutic administration. We also discuss currently available animal models that are used for preclinical assessment of RNA-interference-based gene therapy. Advances in this field have the potential for antiviral treatments of COVID-19 disease and could be adapted to treat a range of respiratory diseases.<\/jats:p>","DOI":"10.3390\/ijms23052408","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T22:34:30Z","timestamp":1645569270000},"page":"2408","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Nanoparticle Delivery Platforms for RNAi Therapeutics Targeting COVID-19 Disease in the Respiratory Tract"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3270-1082","authenticated-orcid":false,"given":"Yuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Kirby Institute, UNSW, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2939-0308","authenticated-orcid":false,"given":"Juhura G.","family":"Almazi","sequence":"additional","affiliation":[{"name":"Respiratory Technology, Woolcock Institute of Medical Research, Sydney, NSW 2037, Australia"},{"name":"Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Ryde, NSW 2109, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Xin","family":"Ong","sequence":"additional","affiliation":[{"name":"Respiratory Technology, Woolcock Institute of Medical Research, Sydney, NSW 2037, Australia"},{"name":"Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Ryde, NSW 2109, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5553-5270","authenticated-orcid":false,"given":"Matt D.","family":"Johansen","sequence":"additional","affiliation":[{"name":"Centre for Inflammation, Faculty of Science, Centenary Institute and University of Technology Sydney, Sydney, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Ledger","sequence":"additional","affiliation":[{"name":"Kirby Institute, UNSW, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7173-017X","authenticated-orcid":false,"given":"Daniela","family":"Traini","sequence":"additional","affiliation":[{"name":"Respiratory Technology, Woolcock Institute of Medical Research, Sydney, NSW 2037, Australia"},{"name":"Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Ryde, NSW 2109, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4741-3035","authenticated-orcid":false,"given":"Philip M.","family":"Hansbro","sequence":"additional","affiliation":[{"name":"Centre for Inflammation, Faculty of Science, Centenary Institute and University of Technology Sydney, Sydney, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony D.","family":"Kelleher","sequence":"additional","affiliation":[{"name":"Kirby Institute, UNSW, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4238-7237","authenticated-orcid":false,"given":"Chantelle L.","family":"Ahlenstiel","sequence":"additional","affiliation":[{"name":"Kirby Institute, UNSW, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1056\/NEJMoa2022483","article-title":"An mRNA Vaccine against SARS-CoV-2\u2014Preliminary Report","volume":"383","author":"Jackson","year":"2020","journal-title":"N. 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