Efficient and targeted delivery of siRNA in vivo
RNA interference (RNAi) has been regarded as a revolutionary tool for manipulating target biological processes as well as an emerging and promising therapeutic strategy. In contrast to the tangible and obvious effectiveness of RNAi in vitro, silencing target gene expression in vivo using small inter...
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| Veröffentlicht in: | The FEBS journal 2010-12, Vol.277 (23), p.4814-4827 |
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| creator | Shim, Min Suk Kwon, Young Jik |
| description | RNA interference (RNAi) has been regarded as a revolutionary tool for manipulating target biological processes as well as an emerging and promising therapeutic strategy. In contrast to the tangible and obvious effectiveness of RNAi in vitro, silencing target gene expression in vivo using small interfering RNA (siRNA) has been a very challenging task due to multiscale barriers, including rapid excretion, low stability in blood serum, nonspecific accumulation in tissues, poor cellular uptake and inefficient intracellular release. This minireview introduces major challenges in achieving efficient siRNA delivery in vivo and discusses recent advances in overcoming them using chemically modified siRNA, viral siRNA vectors and nonviral siRNA carriers. Enhanced specificity and efficiency of RNAi in vivo via selective accumulations in desired tissues, specific binding to target cells and facilitated intracellular trafficking are also commonly attempted utilizing targeting moieties, cell‐penetrating peptides, fusogenic peptides and stimuli‐responsive polymers. Overall, the crucial roles of the interdisciplinary approaches to optimizing RNAi in vivo, by efficiently and specifically delivering siRNA to target tissues and cells, are highlighted. |
| doi_str_mv | 10.1111/j.1742-4658.2010.07904.x |
| format | Article |
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In contrast to the tangible and obvious effectiveness of RNAi in vitro, silencing target gene expression in vivo using small interfering RNA (siRNA) has been a very challenging task due to multiscale barriers, including rapid excretion, low stability in blood serum, nonspecific accumulation in tissues, poor cellular uptake and inefficient intracellular release. This minireview introduces major challenges in achieving efficient siRNA delivery in vivo and discusses recent advances in overcoming them using chemically modified siRNA, viral siRNA vectors and nonviral siRNA carriers. Enhanced specificity and efficiency of RNAi in vivo via selective accumulations in desired tissues, specific binding to target cells and facilitated intracellular trafficking are also commonly attempted utilizing targeting moieties, cell‐penetrating peptides, fusogenic peptides and stimuli‐responsive polymers. 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In contrast to the tangible and obvious effectiveness of RNAi in vitro, silencing target gene expression in vivo using small interfering RNA (siRNA) has been a very challenging task due to multiscale barriers, including rapid excretion, low stability in blood serum, nonspecific accumulation in tissues, poor cellular uptake and inefficient intracellular release. This minireview introduces major challenges in achieving efficient siRNA delivery in vivo and discusses recent advances in overcoming them using chemically modified siRNA, viral siRNA vectors and nonviral siRNA carriers. Enhanced specificity and efficiency of RNAi in vivo via selective accumulations in desired tissues, specific binding to target cells and facilitated intracellular trafficking are also commonly attempted utilizing targeting moieties, cell‐penetrating peptides, fusogenic peptides and stimuli‐responsive polymers. 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Kwon, Young Jik</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5684-c8dfc7467bbcb9131eb4228d274dbee6328b3939b99802a9c83916a3f6d68dcd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>administration routes</topic><topic>Animals</topic><topic>Aptamers, Nucleotide - administration & dosage</topic><topic>barriers in siRNA delivery</topic><topic>Biochemistry</topic><topic>chemically modified RNA</topic><topic>Cholesterol - administration & dosage</topic><topic>Drug Carriers</topic><topic>Drug Delivery Systems</topic><topic>Drug Design</topic><topic>Gene expression</topic><topic>Genetic Engineering</topic><topic>Genetic Therapy - methods</topic><topic>Genetic Vectors</topic><topic>Humans</topic><topic>in vivo disease models</topic><topic>Liposomes</topic><topic>nanoparticles</topic><topic>nonviral carriers</topic><topic>nucleic acid therapeutics</topic><topic>Polymers</topic><topic>Research methodology</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering - administration & dosage</topic><topic>RNA, Small Interfering - genetics</topic><topic>RNA, Small Interfering - therapeutic use</topic><topic>targeted delivery in vivo</topic><topic>viral vectors</topic><topic>Viruses</topic><topic>Viruses - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shim, Min Suk</creatorcontrib><creatorcontrib>Kwon, Young Jik</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The FEBS journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shim, Min Suk</au><au>Kwon, Young Jik</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficient and targeted delivery of siRNA in vivo</atitle><jtitle>The FEBS journal</jtitle><addtitle>FEBS J</addtitle><date>2010-12</date><risdate>2010</risdate><volume>277</volume><issue>23</issue><spage>4814</spage><epage>4827</epage><pages>4814-4827</pages><issn>1742-464X</issn><eissn>1742-4658</eissn><abstract>RNA interference (RNAi) has been regarded as a revolutionary tool for manipulating target biological processes as well as an emerging and promising therapeutic strategy. In contrast to the tangible and obvious effectiveness of RNAi in vitro, silencing target gene expression in vivo using small interfering RNA (siRNA) has been a very challenging task due to multiscale barriers, including rapid excretion, low stability in blood serum, nonspecific accumulation in tissues, poor cellular uptake and inefficient intracellular release. This minireview introduces major challenges in achieving efficient siRNA delivery in vivo and discusses recent advances in overcoming them using chemically modified siRNA, viral siRNA vectors and nonviral siRNA carriers. Enhanced specificity and efficiency of RNAi in vivo via selective accumulations in desired tissues, specific binding to target cells and facilitated intracellular trafficking are also commonly attempted utilizing targeting moieties, cell‐penetrating peptides, fusogenic peptides and stimuli‐responsive polymers. 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| subjects | administration routes Animals Aptamers, Nucleotide - administration & dosage barriers in siRNA delivery Biochemistry chemically modified RNA Cholesterol - administration & dosage Drug Carriers Drug Delivery Systems Drug Design Gene expression Genetic Engineering Genetic Therapy - methods Genetic Vectors Humans in vivo disease models Liposomes nanoparticles nonviral carriers nucleic acid therapeutics Polymers Research methodology Ribonucleic acid RNA RNA Interference RNA, Small Interfering - administration & dosage RNA, Small Interfering - genetics RNA, Small Interfering - therapeutic use targeted delivery in vivo viral vectors Viruses Viruses - genetics |
| title | Efficient and targeted delivery of siRNA in vivo |
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