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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
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 fo...
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Published in: | Molecules (Basel, Switzerland) Switzerland), 2020-04, Vol.25 (7), p.1725 |
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description | 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.
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.
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.
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. |
doi_str_mv | 10.3390/molecules25071725 |
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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.
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.
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.</description><identifier>ISSN: 1420-3049</identifier><identifier>EISSN: 1420-3049</identifier><identifier>DOI: 10.3390/molecules25071725</identifier><identifier>PMID: 32283709</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animals ; cationic liposomes ; Cell Line, Tumor ; Deoxyribonucleic acid ; Disease Models, Animal ; DNA ; Gene Expression ; Gene Silencing ; Humans ; Immunity, Innate - genetics ; Immunomodulation - genetics ; Injection ; innate immunity ; intelligent RNA expression device (iRed) ; Interleukin 6 ; Intravenous administration ; Liposomes ; Mesothelioma ; Mesothelioma, Malignant - genetics ; Mice ; Molecular weight ; Plasmids ; Pleural Neoplasms - genetics ; Polyethylene glycol ; Ratios ; RNA Interference ; RNA, Small Interfering - administration & dosage ; RNA, Small Interfering - genetics ; RNA-mediated interference ; shRNA ; Stimulation ; Transfection ; Xenograft Model Antitumor Assays</subject><ispartof>Molecules (Basel, Switzerland), 2020-04, Vol.25 (7), p.1725</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c603t-9af368a9b3645578c1edb82d9e4b96dde967d6fcbbbf22ab8b0c92f12ba412ef3</citedby><cites>FETCH-LOGICAL-c603t-9af368a9b3645578c1edb82d9e4b96dde967d6fcbbbf22ab8b0c92f12ba412ef3</cites><orcidid>0000-0002-5359-3722 ; 0000-0001-7385-868X ; 0000-0002-8326-2166</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2389466381/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2389466381?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,25732,27903,27904,36991,44569,53769,53771,74872</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32283709$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ando, Hidenori</creatorcontrib><creatorcontrib>Saito-Tarashima, Noriko</creatorcontrib><creatorcontrib>Lila, Amr S Abu</creatorcontrib><creatorcontrib>Kinjo, Nozomi</creatorcontrib><creatorcontrib>Shimizu, Taro</creatorcontrib><creatorcontrib>Ishima, Yu</creatorcontrib><creatorcontrib>Minakawa, Noriaki</creatorcontrib><creatorcontrib>Ishida, Tatsuhiro</creatorcontrib><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</title><title>Molecules (Basel, Switzerland)</title><addtitle>Molecules</addtitle><description>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.
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.
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.
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.</description><subject>Animals</subject><subject>cationic liposomes</subject><subject>Cell Line, Tumor</subject><subject>Deoxyribonucleic acid</subject><subject>Disease Models, Animal</subject><subject>DNA</subject><subject>Gene Expression</subject><subject>Gene Silencing</subject><subject>Humans</subject><subject>Immunity, Innate - genetics</subject><subject>Immunomodulation - genetics</subject><subject>Injection</subject><subject>innate immunity</subject><subject>intelligent RNA expression device (iRed)</subject><subject>Interleukin 6</subject><subject>Intravenous administration</subject><subject>Liposomes</subject><subject>Mesothelioma</subject><subject>Mesothelioma, Malignant - genetics</subject><subject>Mice</subject><subject>Molecular weight</subject><subject>Plasmids</subject><subject>Pleural Neoplasms - genetics</subject><subject>Polyethylene glycol</subject><subject>Ratios</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering - administration & dosage</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA-mediated interference</subject><subject>shRNA</subject><subject>Stimulation</subject><subject>Transfection</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1420-3049</issn><issn>1420-3049</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNplkttuEzEQhlcIRA_wANwgS9yA1IAPe_DeVIpKCZFSQCkRlysfZhNHXnuxd6P2CXktdpNQteLG9nj-_xuPPEnyhuCPjJX4U-MtqN5CpBkuSEGzZ8kpSSmeMJyWzx-dT5KzGLcYU5KS7GVywijlrMDlafJnilbO_O4BzcDB5NZYcMq4NZq2bfBCbS7QKo6xcGjuOrDWrMF1aPltiq7v2gAxGu_QZ9gZBei9WYL-cIGWEHvbRWQcujHONMKiedP0DtBtZ5reim40_dqAQzOzG1Z5jxZejTLXBdFa6MM-2ILaS0eQGEo7MdT-cUzfQPTdBqzxjXiVvKiFjfD6uJ8nqy_XP6--ThbfZ_Or6WKicsy6SSlqlnNRSpanWVZwRUBLTnUJqSxzraHMC53XSkpZUyokl1iVtCZUipRQqNl5Mj9wtRfbqg1Db-G-8sJU-wsf1pUInVEWKtCYS15wkZc65VgKqXSWEWBYa50qGFiXB1bbywa0grF3-wT6NOPMplr7XVUQTmiKB8C7IyD44QtjV219H9zQf0UZL9M8Z5wMKnJQqeBjDFA_VCC4Gueo-m-OBs_bx097cPwbHPYXTovLdg</recordid><startdate>20200409</startdate><enddate>20200409</enddate><creator>Ando, Hidenori</creator><creator>Saito-Tarashima, Noriko</creator><creator>Lila, Amr S Abu</creator><creator>Kinjo, Nozomi</creator><creator>Shimizu, Taro</creator><creator>Ishima, Yu</creator><creator>Minakawa, Noriaki</creator><creator>Ishida, Tatsuhiro</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-5359-3722</orcidid><orcidid>https://orcid.org/0000-0001-7385-868X</orcidid><orcidid>https://orcid.org/0000-0002-8326-2166</orcidid></search><sort><creationdate>20200409</creationdate><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</title><author>Ando, Hidenori ; Saito-Tarashima, Noriko ; Lila, Amr S Abu ; Kinjo, Nozomi ; Shimizu, Taro ; Ishima, Yu ; Minakawa, Noriaki ; Ishida, Tatsuhiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c603t-9af368a9b3645578c1edb82d9e4b96dde967d6fcbbbf22ab8b0c92f12ba412ef3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>cationic liposomes</topic><topic>Cell Line, Tumor</topic><topic>Deoxyribonucleic acid</topic><topic>Disease Models, Animal</topic><topic>DNA</topic><topic>Gene Expression</topic><topic>Gene Silencing</topic><topic>Humans</topic><topic>Immunity, Innate - genetics</topic><topic>Immunomodulation - genetics</topic><topic>Injection</topic><topic>innate immunity</topic><topic>intelligent RNA expression device (iRed)</topic><topic>Interleukin 6</topic><topic>Intravenous administration</topic><topic>Liposomes</topic><topic>Mesothelioma</topic><topic>Mesothelioma, Malignant - genetics</topic><topic>Mice</topic><topic>Molecular weight</topic><topic>Plasmids</topic><topic>Pleural Neoplasms - genetics</topic><topic>Polyethylene glycol</topic><topic>Ratios</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering - administration & dosage</topic><topic>RNA, Small Interfering - genetics</topic><topic>RNA-mediated interference</topic><topic>shRNA</topic><topic>Stimulation</topic><topic>Transfection</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ando, Hidenori</creatorcontrib><creatorcontrib>Saito-Tarashima, Noriko</creatorcontrib><creatorcontrib>Lila, Amr S Abu</creatorcontrib><creatorcontrib>Kinjo, Nozomi</creatorcontrib><creatorcontrib>Shimizu, Taro</creatorcontrib><creatorcontrib>Ishima, Yu</creatorcontrib><creatorcontrib>Minakawa, Noriaki</creatorcontrib><creatorcontrib>Ishida, Tatsuhiro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Molecules (Basel, Switzerland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ando, Hidenori</au><au>Saito-Tarashima, Noriko</au><au>Lila, Amr S Abu</au><au>Kinjo, Nozomi</au><au>Shimizu, Taro</au><au>Ishima, Yu</au><au>Minakawa, Noriaki</au><au>Ishida, Tatsuhiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Molecules (Basel, Switzerland)</jtitle><addtitle>Molecules</addtitle><date>2020-04-09</date><risdate>2020</risdate><volume>25</volume><issue>7</issue><spage>1725</spage><pages>1725-</pages><issn>1420-3049</issn><eissn>1420-3049</eissn><abstract>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.
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.
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.
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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>32283709</pmid><doi>10.3390/molecules25071725</doi><orcidid>https://orcid.org/0000-0002-5359-3722</orcidid><orcidid>https://orcid.org/0000-0001-7385-868X</orcidid><orcidid>https://orcid.org/0000-0002-8326-2166</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Animals cationic liposomes Cell Line, Tumor Deoxyribonucleic acid Disease Models, Animal DNA Gene Expression Gene Silencing Humans Immunity, Innate - genetics Immunomodulation - genetics Injection innate immunity intelligent RNA expression device (iRed) Interleukin 6 Intravenous administration Liposomes Mesothelioma Mesothelioma, Malignant - genetics Mice Molecular weight Plasmids Pleural Neoplasms - genetics Polyethylene glycol Ratios RNA Interference RNA, Small Interfering - administration & dosage RNA, Small Interfering - genetics RNA-mediated interference shRNA Stimulation Transfection Xenograft Model Antitumor Assays |
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 |
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