A novel siRNA-lipoplex technology for RNA interference in the mouse vascular endothelium
For the application of RNA interference (RNAi) in vivo the functional delivery of short interfering RNAs (siRNAs) is still the major obstacle. Therefore, delivery technologies need to be established for the systemic application of RNAi in vivo . Here we report uptake, biodistribution and in vivo eff...
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| Veröffentlicht in: | Gene therapy 2006-08, Vol.13 (16), p.1222-1234 |
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| creator | Santel, A Aleku, M Keil, O Endruschat, J Esche, V Fisch, G Dames, S Löffler, K Fechtner, M Arnold, W Giese, K Klippel, A Kaufmann, J |
| description | For the application of RNA interference (RNAi)
in vivo
the functional delivery of short interfering RNAs (siRNAs) is still the major obstacle. Therefore, delivery technologies need to be established for the systemic application of RNAi
in vivo
. Here we report uptake, biodistribution and
in vivo
efficacy of siRNA molecules formulated into siRNA-lipoplexes. The applied formulation is based on complex formation of positively charged liposomes, a mixture of cationic and fusogenic lipids complexed with the negatively charged siRNA. We determined by fluorescence microscopy the temporal and spatial distribution of fluorescently labeled siRNA-lipoplexes, the body clearance and endothelial cell type specific uptake after single intravenous injection. Furthermore, by using siRNA molecules for targeting endothelia-specifically expressed genes, such as
CD31
and
Tie2
, we were able to demonstrate downregulation of the corresponding mRNA and protein
in vivo
. Taken together, we show the applicability of this non-viral delivery technology for inducing RNAi in the vasculature of mice after systemic application. |
| doi_str_mv | 10.1038/sj.gt.3302777 |
| format | Article |
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in vivo
the functional delivery of short interfering RNAs (siRNAs) is still the major obstacle. Therefore, delivery technologies need to be established for the systemic application of RNAi
in vivo
. Here we report uptake, biodistribution and
in vivo
efficacy of siRNA molecules formulated into siRNA-lipoplexes. The applied formulation is based on complex formation of positively charged liposomes, a mixture of cationic and fusogenic lipids complexed with the negatively charged siRNA. We determined by fluorescence microscopy the temporal and spatial distribution of fluorescently labeled siRNA-lipoplexes, the body clearance and endothelial cell type specific uptake after single intravenous injection. Furthermore, by using siRNA molecules for targeting endothelia-specifically expressed genes, such as
CD31
and
Tie2
, we were able to demonstrate downregulation of the corresponding mRNA and protein
in vivo
. Taken together, we show the applicability of this non-viral delivery technology for inducing RNAi in the vasculature of mice after systemic application.</description><identifier>ISSN: 0969-7128</identifier><identifier>EISSN: 1476-5462</identifier><identifier>DOI: 10.1038/sj.gt.3302777</identifier><identifier>PMID: 16625243</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Applied cell therapy and gene therapy ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Biotechnology ; Cell Biology ; Cell differentiation, maturation, development, hematopoiesis ; Cell Line, Tumor ; Cell physiology ; Circulatory system ; Down-Regulation ; Endothelial cells ; Endothelial Cells - metabolism ; Endothelium ; Endothelium, Vascular - metabolism ; Fluorescence microscopy ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; Gene Therapy ; Genetic Therapy - methods ; Health. Pharmaceutical industry ; Human Genetics ; Humans ; Immunohistochemistry - methods ; Industrial applications and implications. Economical aspects ; Injections, Intravenous ; Interleukin-12 - blood ; Intravenous administration ; Kidney - metabolism ; Lipids ; Liposomes ; Male ; Medical sciences ; Mice ; Mice, Nude ; Microscopy, Fluorescence ; Molecular and cellular biology ; mRNA ; Nanotechnology ; original-article ; Pharmacokinetics ; Platelet Endothelial Cell Adhesion Molecule-1 - blood ; Platelet Endothelial Cell Adhesion Molecule-1 - genetics ; Polyethyleneimine ; Receptor, TIE-2 - blood ; Receptor, TIE-2 - genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Ribonucleic acid ; RNA ; RNA Interference ; RNA, Messenger - analysis ; RNA, Small Interfering - administration & dosage ; RNA, Small Interfering - genetics ; RNA, Small Interfering - metabolism ; RNA-mediated interference ; Rodents ; siRNA ; Spatial distribution ; Transfection - methods ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><ispartof>Gene therapy, 2006-08, Vol.13 (16), p.1222-1234</ispartof><rights>Springer Nature Limited 2006</rights><rights>2006 INIST-CNRS</rights><rights>COPYRIGHT 2006 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Aug 2006</rights><rights>Nature Publishing Group 2006.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c683t-c7d1eddc78a25fe02e18f6c9062139460c0d6b7ec77babf474b7be7cb3f379873</citedby><cites>FETCH-LOGICAL-c683t-c7d1eddc78a25fe02e18f6c9062139460c0d6b7ec77babf474b7be7cb3f379873</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.gt.3302777$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.gt.3302777$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17994325$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16625243$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Santel, A</creatorcontrib><creatorcontrib>Aleku, M</creatorcontrib><creatorcontrib>Keil, O</creatorcontrib><creatorcontrib>Endruschat, J</creatorcontrib><creatorcontrib>Esche, V</creatorcontrib><creatorcontrib>Fisch, G</creatorcontrib><creatorcontrib>Dames, S</creatorcontrib><creatorcontrib>Löffler, K</creatorcontrib><creatorcontrib>Fechtner, M</creatorcontrib><creatorcontrib>Arnold, W</creatorcontrib><creatorcontrib>Giese, K</creatorcontrib><creatorcontrib>Klippel, A</creatorcontrib><creatorcontrib>Kaufmann, J</creatorcontrib><title>A novel siRNA-lipoplex technology for RNA interference in the mouse vascular endothelium</title><title>Gene therapy</title><addtitle>Gene Ther</addtitle><addtitle>Gene Ther</addtitle><description>For the application of RNA interference (RNAi)
in vivo
the functional delivery of short interfering RNAs (siRNAs) is still the major obstacle. Therefore, delivery technologies need to be established for the systemic application of RNAi
in vivo
. Here we report uptake, biodistribution and
in vivo
efficacy of siRNA molecules formulated into siRNA-lipoplexes. The applied formulation is based on complex formation of positively charged liposomes, a mixture of cationic and fusogenic lipids complexed with the negatively charged siRNA. We determined by fluorescence microscopy the temporal and spatial distribution of fluorescently labeled siRNA-lipoplexes, the body clearance and endothelial cell type specific uptake after single intravenous injection. Furthermore, by using siRNA molecules for targeting endothelia-specifically expressed genes, such as
CD31
and
Tie2
, we were able to demonstrate downregulation of the corresponding mRNA and protein
in vivo
. Taken together, we show the applicability of this non-viral delivery technology for inducing RNAi in the vasculature of mice after systemic application.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Applied cell therapy and gene therapy</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Cell Biology</subject><subject>Cell differentiation, maturation, development, hematopoiesis</subject><subject>Cell Line, Tumor</subject><subject>Cell physiology</subject><subject>Circulatory system</subject><subject>Down-Regulation</subject><subject>Endothelial cells</subject><subject>Endothelial Cells - metabolism</subject><subject>Endothelium</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Fluorescence microscopy</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>Gene Therapy</subject><subject>Genetic Therapy - methods</subject><subject>Health. Pharmaceutical industry</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Immunohistochemistry - methods</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Injections, Intravenous</subject><subject>Interleukin-12 - blood</subject><subject>Intravenous administration</subject><subject>Kidney - metabolism</subject><subject>Lipids</subject><subject>Liposomes</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Microscopy, Fluorescence</subject><subject>Molecular and cellular biology</subject><subject>mRNA</subject><subject>Nanotechnology</subject><subject>original-article</subject><subject>Pharmacokinetics</subject><subject>Platelet Endothelial Cell Adhesion Molecule-1 - blood</subject><subject>Platelet Endothelial Cell Adhesion Molecule-1 - genetics</subject><subject>Polyethyleneimine</subject><subject>Receptor, TIE-2 - blood</subject><subject>Receptor, TIE-2 - genetics</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA Interference</subject><subject>RNA, Messenger - analysis</subject><subject>RNA, Small Interfering - administration & dosage</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA, Small Interfering - metabolism</subject><subject>RNA-mediated interference</subject><subject>Rodents</subject><subject>siRNA</subject><subject>Spatial distribution</subject><subject>Transfection - methods</subject><subject>Transfusions. Complications. Transfusion reactions. 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Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Applied cell therapy and gene therapy</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Cell Biology</topic><topic>Cell differentiation, maturation, development, hematopoiesis</topic><topic>Cell Line, Tumor</topic><topic>Cell physiology</topic><topic>Circulatory system</topic><topic>Down-Regulation</topic><topic>Endothelial cells</topic><topic>Endothelial Cells - metabolism</topic><topic>Endothelium</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Fluorescence microscopy</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression</topic><topic>Gene Therapy</topic><topic>Genetic Therapy - methods</topic><topic>Health. Pharmaceutical industry</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Immunohistochemistry - methods</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Injections, Intravenous</topic><topic>Interleukin-12 - blood</topic><topic>Intravenous administration</topic><topic>Kidney - metabolism</topic><topic>Lipids</topic><topic>Liposomes</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Microscopy, Fluorescence</topic><topic>Molecular and cellular biology</topic><topic>mRNA</topic><topic>Nanotechnology</topic><topic>original-article</topic><topic>Pharmacokinetics</topic><topic>Platelet Endothelial Cell Adhesion Molecule-1 - blood</topic><topic>Platelet Endothelial Cell Adhesion Molecule-1 - genetics</topic><topic>Polyethyleneimine</topic><topic>Receptor, TIE-2 - blood</topic><topic>Receptor, TIE-2 - genetics</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA Interference</topic><topic>RNA, Messenger - analysis</topic><topic>RNA, Small Interfering - administration & dosage</topic><topic>RNA, Small Interfering - genetics</topic><topic>RNA, Small Interfering - metabolism</topic><topic>RNA-mediated interference</topic><topic>Rodents</topic><topic>siRNA</topic><topic>Spatial distribution</topic><topic>Transfection - methods</topic><topic>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Santel, A</creatorcontrib><creatorcontrib>Aleku, M</creatorcontrib><creatorcontrib>Keil, O</creatorcontrib><creatorcontrib>Endruschat, J</creatorcontrib><creatorcontrib>Esche, V</creatorcontrib><creatorcontrib>Fisch, G</creatorcontrib><creatorcontrib>Dames, S</creatorcontrib><creatorcontrib>Löffler, K</creatorcontrib><creatorcontrib>Fechtner, M</creatorcontrib><creatorcontrib>Arnold, W</creatorcontrib><creatorcontrib>Giese, K</creatorcontrib><creatorcontrib>Klippel, A</creatorcontrib><creatorcontrib>Kaufmann, J</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database (Proquest)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest research library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</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>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Santel, A</au><au>Aleku, M</au><au>Keil, O</au><au>Endruschat, J</au><au>Esche, V</au><au>Fisch, G</au><au>Dames, S</au><au>Löffler, K</au><au>Fechtner, M</au><au>Arnold, W</au><au>Giese, K</au><au>Klippel, A</au><au>Kaufmann, J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel siRNA-lipoplex technology for RNA interference in the mouse vascular endothelium</atitle><jtitle>Gene therapy</jtitle><stitle>Gene Ther</stitle><addtitle>Gene Ther</addtitle><date>2006-08-01</date><risdate>2006</risdate><volume>13</volume><issue>16</issue><spage>1222</spage><epage>1234</epage><pages>1222-1234</pages><issn>0969-7128</issn><eissn>1476-5462</eissn><abstract>For the application of RNA interference (RNAi)
in vivo
the functional delivery of short interfering RNAs (siRNAs) is still the major obstacle. Therefore, delivery technologies need to be established for the systemic application of RNAi
in vivo
. Here we report uptake, biodistribution and
in vivo
efficacy of siRNA molecules formulated into siRNA-lipoplexes. The applied formulation is based on complex formation of positively charged liposomes, a mixture of cationic and fusogenic lipids complexed with the negatively charged siRNA. We determined by fluorescence microscopy the temporal and spatial distribution of fluorescently labeled siRNA-lipoplexes, the body clearance and endothelial cell type specific uptake after single intravenous injection. Furthermore, by using siRNA molecules for targeting endothelia-specifically expressed genes, such as
CD31
and
Tie2
, we were able to demonstrate downregulation of the corresponding mRNA and protein
in vivo
. Taken together, we show the applicability of this non-viral delivery technology for inducing RNAi in the vasculature of mice after systemic application.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>16625243</pmid><doi>10.1038/sj.gt.3302777</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0969-7128 |
| ispartof | Gene therapy, 2006-08, Vol.13 (16), p.1222-1234 |
| issn | 0969-7128 1476-5462 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68731477 |
| source | MEDLINE; SpringerLink (Online service); EZB Electronic Journals Library |
| subjects | Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Applied cell therapy and gene therapy Biological and medical sciences Biomedical and Life Sciences Biomedicine Biotechnology Cell Biology Cell differentiation, maturation, development, hematopoiesis Cell Line, Tumor Cell physiology Circulatory system Down-Regulation Endothelial cells Endothelial Cells - metabolism Endothelium Endothelium, Vascular - metabolism Fluorescence microscopy Fundamental and applied biological sciences. Psychology Gene Expression Gene Therapy Genetic Therapy - methods Health. Pharmaceutical industry Human Genetics Humans Immunohistochemistry - methods Industrial applications and implications. Economical aspects Injections, Intravenous Interleukin-12 - blood Intravenous administration Kidney - metabolism Lipids Liposomes Male Medical sciences Mice Mice, Nude Microscopy, Fluorescence Molecular and cellular biology mRNA Nanotechnology original-article Pharmacokinetics Platelet Endothelial Cell Adhesion Molecule-1 - blood Platelet Endothelial Cell Adhesion Molecule-1 - genetics Polyethyleneimine Receptor, TIE-2 - blood Receptor, TIE-2 - genetics Reverse Transcriptase Polymerase Chain Reaction Ribonucleic acid RNA RNA Interference RNA, Messenger - analysis RNA, Small Interfering - administration & dosage RNA, Small Interfering - genetics RNA, Small Interfering - metabolism RNA-mediated interference Rodents siRNA Spatial distribution Transfection - methods Transfusions. Complications. Transfusion reactions. Cell and gene therapy |
| title | A novel siRNA-lipoplex technology for RNA interference in the mouse vascular endothelium |
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