Design and Creation of New Nanomaterials for Therapeutic RNAi
RNA interference is an evolutionarily conserved gene-silencing phenomenon that shows great promise for developing new therapies. However, the development of small interfering RNA (siRNA)-based therapies needs to overcome two barriers and be able to (i) identify chemically stable and effective siRNA...
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| Veröffentlicht in: | ACS chemical biology 2007-04, Vol.2 (4), p.237-241 |
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| creator | Baigude, Huricha McCarroll, Joshua Yang, Chao-shun Swain, Pamela M Rana, Tariq M |
| description | RNA interference is an evolutionarily conserved gene-silencing phenomenon that shows great promise for developing new therapies. However, the development of small interfering RNA (siRNA)-based therapies needs to overcome two barriers and be able to (i) identify chemically stable and effective siRNA sequences and (ii) efficiently silence target genes with siRNA doses that will be clinically feasible in humans. Here, we report the design and creation of interfering nanoparticles (iNOPs) as new systemic gene-silencing agents. iNOPs have two subunits: (i) a well-defined functionalized lipid nanoparticle as a delivery agent and (ii) a chemically modified siRNA for sustained silencing in vivo. When we injected iNOPs containing only 1−5 mg kg–1 siRNA into mice, an endogenous gene for apolipoprotein B (apoB) was silenced in liver, plasma levels of apoB decreased, and total plasma cholesterol was lowered. iNOP treatment was nontoxic and did not induce an immune response. Our results show that these iNOPs can silence disease-related endogenous genes in clinically acceptable and therapeutically affordable doses. |
| doi_str_mv | 10.1021/cb7000582 |
| format | Article |
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When we injected iNOPs containing only 1−5 mg kg–1 siRNA into mice, an endogenous gene for apolipoprotein B (apoB) was silenced in liver, plasma levels of apoB decreased, and total plasma cholesterol was lowered. iNOP treatment was nontoxic and did not induce an immune response. Our results show that these iNOPs can silence disease-related endogenous genes in clinically acceptable and therapeutically affordable doses.</description><subject>Animals</subject><subject>Apolipoproteins B - blood</subject><subject>Apolipoproteins B - genetics</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Nanoparticles - chemistry</subject><subject>Nanoparticles - therapeutic use</subject><subject>Peptide Fragments - blood</subject><subject>Peptide Fragments - genetics</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering - therapeutic use</subject><issn>1554-8929</issn><issn>1554-8937</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkE1LAzEURYMotlYX_gHJRsHFaD4mk2ThooyfUCpIXYdkJtGUzqQmM4j_3iktdePqPXiHy7sHgHOMbjAi-LYyHCHEBDkAY8xYnglJ-eF-J3IETlJaIpTTQshjMMI8p0QQOgZ39zb5jxbqtoZltLrzoYXBwbn9hnPdhkZ3Nnq9StCFCBefNuq17Ttfwbf51J-CIzfc7NluTsD748OifM5mr08v5XSWacpll5FcD29KxpiQTOaOGiwqUtSFrREpuMGWOEc1k44b6ggWqBA1MtpoYRBxkk7A1TZ3HcNXb1OnGp8qu1rp1oY-Kb5pxnM0gNdbsIohpWidWkff6PijMFIbV2rvamAvdqG9aWz9R-7kDMDlFtBVUsvQx3bo-E_QLxNVbXo</recordid><startdate>20070401</startdate><enddate>20070401</enddate><creator>Baigude, Huricha</creator><creator>McCarroll, Joshua</creator><creator>Yang, Chao-shun</creator><creator>Swain, Pamela M</creator><creator>Rana, Tariq M</creator><general>American Chemical Society</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>7X8</scope></search><sort><creationdate>20070401</creationdate><title>Design and Creation of New Nanomaterials for Therapeutic RNAi</title><author>Baigude, Huricha ; McCarroll, Joshua ; Yang, Chao-shun ; Swain, Pamela M ; Rana, Tariq M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a379t-24a021955589594f3b18c26d6ed0267b1e2ff3a59f7b3f218068d0baba8b02f93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Apolipoproteins B - blood</topic><topic>Apolipoproteins B - genetics</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Nanoparticles - chemistry</topic><topic>Nanoparticles - therapeutic use</topic><topic>Peptide Fragments - blood</topic><topic>Peptide Fragments - genetics</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Baigude, Huricha</creatorcontrib><creatorcontrib>McCarroll, Joshua</creatorcontrib><creatorcontrib>Yang, Chao-shun</creatorcontrib><creatorcontrib>Swain, Pamela M</creatorcontrib><creatorcontrib>Rana, Tariq M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>ACS chemical biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Baigude, Huricha</au><au>McCarroll, Joshua</au><au>Yang, Chao-shun</au><au>Swain, Pamela M</au><au>Rana, Tariq M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design and Creation of New Nanomaterials for Therapeutic RNAi</atitle><jtitle>ACS chemical biology</jtitle><addtitle>ACS Chem. 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| ispartof | ACS chemical biology, 2007-04, Vol.2 (4), p.237-241 |
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| language | eng |
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| source | ACS Publications; MEDLINE |
| subjects | Animals Apolipoproteins B - blood Apolipoproteins B - genetics Liver - metabolism Male Mice Mice, Inbred C57BL Nanoparticles - chemistry Nanoparticles - therapeutic use Peptide Fragments - blood Peptide Fragments - genetics RNA Interference RNA, Small Interfering - therapeutic use |
| title | Design and Creation of New Nanomaterials for Therapeutic RNAi |
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