Cellular uptake and intracellular release are major obstacles to the therapeutic application of siRNA: novel options by phosphorothioate-stimulated delivery
The cellular uptake of oligomeric nucleic acid-based tools and drugs including small-interfering RNA (siRNA) represents a major technical hurdle for the biologic effectiveness and therapeutic success in vivo. Subsequent to cellular delivery it is crucial to direct siRNA to the cellular location wher...
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| Veröffentlicht in: | Expert opinion on biological therapy 2007-10, Vol.7 (10), p.1531-1538 |
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| container_issue | 10 |
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| container_title | Expert opinion on biological therapy |
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| creator | Mescalchin, Alessandra Detzer, Anke Wecke, Maria Overhoff, Marita Wünsche, Winfried Sczakiel, Georg |
| description | The cellular uptake of oligomeric nucleic acid-based tools and drugs including small-interfering RNA (siRNA) represents a major technical hurdle for the biologic effectiveness and therapeutic success in vivo. Subsequent to cellular delivery it is crucial to direct siRNA to the cellular location where it enters the RNA interference pathway. Here the authors summarise evidence that functionally active siRNA represents a minor fraction in the order of 1% of total siRNA inside a given target cell. Exploiting possibilities of steering intracellular release or trafficking of siRNA bears the potential of substantially increasing the biological activity of siRNA. The recently described phosphorothioate stimulated cellular delivery of siRNA makes use of the caveolar system ending in the Golgi apparatus, which contrasts all other known delivery systems. Therefore, it represents an attractive alternative to study whether promoted intracellular release is related to increased target suppression and, thus, increased phenotypic biologic effectiveness. |
| doi_str_mv | 10.1517/14712598.7.10.1531 |
| format | Article |
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Therefore, it represents an attractive alternative to study whether promoted intracellular release is related to increased target suppression and, thus, increased phenotypic biologic effectiveness.</description><subject>Animals</subject><subject>Biological Transport</subject><subject>caveolae</subject><subject>Caveolae - metabolism</subject><subject>cellular uptake</subject><subject>delivery</subject><subject>Gene Transfer Techniques</subject><subject>Genetic Therapy - methods</subject><subject>Golgi Apparatus - metabolism</subject><subject>Humans</subject><subject>intracellular release</subject><subject>phosphorothioate</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering - metabolism</subject><subject>siRNA</subject><subject>Thionucleotides - metabolism</subject><issn>1471-2598</issn><issn>1744-7682</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kctu1DAUhiMEohd4ARbIK3YZ7MQZOwgW1YgCUgUSgrV1Yp8oHpw42E6reRceFqczFWLTxZGt_3znYv9F8YrRDWuYeMu4YFXTyo3Y3Es1e1KcM8F5KbayeprvGShX4qy4iHFPaUXbpnpenDHRsi3lzXnxZ4fOLQ4CWeYEv5DAZIidUgD9kAjoEGLOBCQj7H0gvosJtMNIkidpwDUCzLgkqwnMs7MakvUT8T2J9vvXq3dk8rfoiJ9XOZLuQObBxxzBp8F6SFjGZMc8L6EhBp29xXB4UTzrwUV8eTovi5_XH3_sPpc33z592V3dlJoLnsq-4lRSyqnhUCEKpiX0yIXpmGBt3aDhkjLJuQTTmU7UDdO0BSZbobWUVX1ZvDn2nYP_vWBMarRxfT9M6JeotrJuaFWzDFZHUAcfY8BezcGOEA6KUbV6oh48UeIo3Re9PnVfuhHNv5KTCRn4cATs1Pswwp0PzqgEB-dDH2DSNqr60QHv_6sfEFwadPZL7f0Spvx1j-33FwxtshA</recordid><startdate>20071001</startdate><enddate>20071001</enddate><creator>Mescalchin, Alessandra</creator><creator>Detzer, Anke</creator><creator>Wecke, Maria</creator><creator>Overhoff, Marita</creator><creator>Wünsche, Winfried</creator><creator>Sczakiel, Georg</creator><general>Informa UK Ltd</general><general>Taylor & Francis</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>20071001</creationdate><title>Cellular uptake and intracellular release are major obstacles to the therapeutic application of siRNA: novel options by phosphorothioate-stimulated delivery</title><author>Mescalchin, Alessandra ; Detzer, Anke ; Wecke, Maria ; Overhoff, Marita ; Wünsche, Winfried ; Sczakiel, Georg</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-f24080040d4a2ee71c8afe47db171935ed48018448adbdb7351c09a1897cc8823</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Biological Transport</topic><topic>caveolae</topic><topic>Caveolae - metabolism</topic><topic>cellular uptake</topic><topic>delivery</topic><topic>Gene Transfer Techniques</topic><topic>Genetic Therapy - methods</topic><topic>Golgi Apparatus - metabolism</topic><topic>Humans</topic><topic>intracellular release</topic><topic>phosphorothioate</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering - metabolism</topic><topic>siRNA</topic><topic>Thionucleotides - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mescalchin, Alessandra</creatorcontrib><creatorcontrib>Detzer, Anke</creatorcontrib><creatorcontrib>Wecke, Maria</creatorcontrib><creatorcontrib>Overhoff, Marita</creatorcontrib><creatorcontrib>Wünsche, Winfried</creatorcontrib><creatorcontrib>Sczakiel, Georg</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>Expert opinion on biological therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mescalchin, Alessandra</au><au>Detzer, Anke</au><au>Wecke, Maria</au><au>Overhoff, Marita</au><au>Wünsche, Winfried</au><au>Sczakiel, Georg</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cellular uptake and intracellular release are major obstacles to the therapeutic application of siRNA: novel options by phosphorothioate-stimulated delivery</atitle><jtitle>Expert opinion on biological therapy</jtitle><addtitle>Expert Opin Biol Ther</addtitle><date>2007-10-01</date><risdate>2007</risdate><volume>7</volume><issue>10</issue><spage>1531</spage><epage>1538</epage><pages>1531-1538</pages><issn>1471-2598</issn><eissn>1744-7682</eissn><abstract>The cellular uptake of oligomeric nucleic acid-based tools and drugs including small-interfering RNA (siRNA) represents a major technical hurdle for the biologic effectiveness and therapeutic success in vivo. 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| fulltext | fulltext |
| identifier | ISSN: 1471-2598 |
| ispartof | Expert opinion on biological therapy, 2007-10, Vol.7 (10), p.1531-1538 |
| issn | 1471-2598 1744-7682 |
| language | eng |
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| source | MEDLINE; Taylor & Francis:Master (3349 titles); Taylor & Francis Medical Library - CRKN |
| subjects | Animals Biological Transport caveolae Caveolae - metabolism cellular uptake delivery Gene Transfer Techniques Genetic Therapy - methods Golgi Apparatus - metabolism Humans intracellular release phosphorothioate RNA Interference RNA, Small Interfering - metabolism siRNA Thionucleotides - metabolism |
| title | Cellular uptake and intracellular release are major obstacles to the therapeutic application of siRNA: novel options by phosphorothioate-stimulated delivery |
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