{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T03:45:05Z","timestamp":1778557505784,"version":"3.51.4"},"reference-count":34,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T00:00:00Z","timestamp":1586390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K16415"],"award-info":[{"award-number":["19K16415"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005623","name":"University of Tokushima","doi-asserted-by":"publisher","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/501100005623","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Background: We have recently introduced an intelligent RNA expression device (iRed), comprising the minimum essential components needed to transcribe short hairpin RNA (shRNA) in cells. Use of iRed efficiently produced shRNA molecules after transfection into cells and alleviated the innate immune stimulation following intravenous injection. Methods: To study the usefulness of iRed for local injection, the engineered iRed encoding luciferase shRNA (Luc iRed), complexed with cationic liposomes (Luc iRed\/liposome-complexes), was intrapleurally injected into an orthotopic mesothelioma mouse model. Results: Luc iRed\/liposome-complexes markedly suppressed the expression of a luciferase marker gene in pleurally disseminated mesothelioma cells. The suppressive efficiency was correlated with the expression level of shRNA within the mesothelioma cells. In addition, intrapleural injection of iRed\/liposome-complexes did not induce IL-6 production in the pleural space and consequently in the blood compartment, although plasmid DNA (pDNA) or dsDNA (the natural construct for iRed) in the formulation did. Conclusion: Local delivery of iRed could augment the in vivo gene silencing effect without eliciting pronounced innate immune stimulation. Our results might hold promise for widespread utilization of iRed as an RNAi-based therapeutic for intracelial malignant cancers.<\/jats:p>","DOI":"10.3390\/molecules25071725","type":"journal-article","created":{"date-parts":[[2020,4,10]],"date-time":"2020-04-10T05:31:16Z","timestamp":1586496676000},"page":"1725","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Unique Gene-Silencing Approach, Using an Intelligent RNA Expression Device (iRed), Results in Minimal Immune Stimulation When Given by Local Intrapleural Injection in Malignant Pleural Mesothelioma"],"prefix":"10.3390","volume":"25","author":[{"given":"Hidenori","family":"Ando","sequence":"first","affiliation":[{"name":"Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriko","family":"Saito-Tarashima","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Chemistry, Institute of Biomedical Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7385-868X","authenticated-orcid":false,"given":"Amr S. Abu","family":"Lila","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt"},{"name":"Department of Pharmaceutics, College of Pharmacy, Hail University, Hail 81442, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nozomi","family":"Kinjo","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8326-2166","authenticated-orcid":false,"given":"Taro","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5359-3722","authenticated-orcid":false,"given":"Yu","family":"Ishima","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriaki","family":"Minakawa","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Chemistry, Institute of Biomedical Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuhiro","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1365-2567.2007.02599.x","article-title":"Immunological research using RNA interference technology","volume":"121","author":"Mao","year":"2007","journal-title":"Immunology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5254","DOI":"10.3390\/ijms16035254","article-title":"Development of small RNA delivery systems for lung cancer therapy","volume":"16","author":"Fujita","year":"2015","journal-title":"Int. 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