RNA interference in the mouse vascular endothelium by systemic administration of siRNA-lipoplexes for cancer therapy
RNA interference (RNAi) entails the potential for novel therapeutic strategies through the silencing of disease-causing genes in vivo . However, recent studies have raised an issue regarding applicable routes of administration for small interfering RNA (siRNA) molecules as therapeutics. In this stud...
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| Veröffentlicht in: | Gene therapy 2006-09, Vol.13 (18), p.1360-1370 |
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| creator | Santel, A Aleku, M Keil, O Endruschat, J Esche, V Durieux, B Löffler, K Fechtner, M Röhl, T Fisch, G Dames, S Arnold, W Giese, K Klippel, A Kaufmann, J |
| description | RNA interference (RNAi) entails the potential for novel therapeutic strategies through the silencing of disease-causing genes
in vivo
. However, recent studies have raised an issue regarding applicable routes of administration for small interfering RNA (siRNA) molecules as therapeutics. In this study, we demonstrate that liposomally formulated siRNA molecules, the so-called siRNA-lipoplexes, but not naked siRNAs, are delivered to the tumor endothelial cells
in vivo
by microscopy. In addition, functional intracellular delivery of formulated siRNA targeting the tumor suppressor PTEN is shown in endothelial cells of the liver and tumor. Finally, the therapeutic potential of systemically administered siRNA
CD31
-lipoplexes is established by inhibition of tumor growth in two different xenograft mouse models. Our findings corroborate the applicability of this liposomal siRNA delivery technology for inducing RNAi to modulate gene expression levels in angiogenesis-dependent processes. In addition, our results advocate CD31 as a promising therapeutic target for antiangiogenic intervention. Therefore, our study provides a basis for the development of antiangiogenic cancer therapies based on RNAi. |
| doi_str_mv | 10.1038/sj.gt.3302778 |
| format | Article |
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in vivo
. However, recent studies have raised an issue regarding applicable routes of administration for small interfering RNA (siRNA) molecules as therapeutics. In this study, we demonstrate that liposomally formulated siRNA molecules, the so-called siRNA-lipoplexes, but not naked siRNAs, are delivered to the tumor endothelial cells
in vivo
by microscopy. In addition, functional intracellular delivery of formulated siRNA targeting the tumor suppressor PTEN is shown in endothelial cells of the liver and tumor. Finally, the therapeutic potential of systemically administered siRNA
CD31
-lipoplexes is established by inhibition of tumor growth in two different xenograft mouse models. Our findings corroborate the applicability of this liposomal siRNA delivery technology for inducing RNAi to modulate gene expression levels in angiogenesis-dependent processes. In addition, our results advocate CD31 as a promising therapeutic target for antiangiogenic intervention. Therefore, our study provides a basis for the development of antiangiogenic cancer therapies based on RNAi.</description><identifier>ISSN: 0969-7128</identifier><identifier>EISSN: 1476-5462</identifier><identifier>DOI: 10.1038/sj.gt.3302778</identifier><identifier>PMID: 16625242</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>3T3 Cells ; Angiogenesis ; Animal models ; Animals ; Antigens, CD34 - genetics ; Antigens, CD34 - metabolism ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer ; Cancer therapies ; Care and treatment ; Cell Biology ; Cell differentiation, maturation, development, hematopoiesis ; Cell Line ; Cell Line, Tumor ; Cell physiology ; Chemotherapy ; Drug Administration Schedule ; Endothelial cells ; Endothelium ; Endothelium, Vascular - immunology ; Endothelium, Vascular - metabolism ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; Gene Silencing ; Gene Therapy ; Genetic aspects ; Genetic Therapy - methods ; Hepatocytes ; Human Genetics ; Humans ; Injections, Intravenous ; Liposomes - administration & dosage ; Male ; Methods ; Mice ; Mice, Nude ; Molecular and cellular biology ; Nanotechnology ; Neoplasm Transplantation ; original-article ; Physiological aspects ; Platelet Endothelial Cell Adhesion Molecule-1 - genetics ; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism ; Prostatic Neoplasms - immunology ; Prostatic Neoplasms - metabolism ; Prostatic Neoplasms - therapy ; PTEN Phosphohydrolase - genetics ; PTEN Phosphohydrolase - metabolism ; PTEN protein ; Ribonucleic acid ; RNA ; RNA Interference ; RNA, Small Interfering - administration & dosage ; RNA-mediated interference ; Rodents ; siRNA ; Therapeutic targets ; Transplantation, Heterologous ; Tumor suppressor genes ; Tumors ; Xenografts</subject><ispartof>Gene therapy, 2006-09, Vol.13 (18), p.1360-1370</ispartof><rights>Springer Nature Limited 2006</rights><rights>2006 INIST-CNRS</rights><rights>COPYRIGHT 2006 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Sep 2006</rights><rights>Nature Publishing Group 2006.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c582t-9b3a227c7727a4418ff19f170fe6c1672bc4a20aeb13fbfe3b7a764be219c6e63</citedby><cites>FETCH-LOGICAL-c582t-9b3a227c7727a4418ff19f170fe6c1672bc4a20aeb13fbfe3b7a764be219c6e63</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.3302778$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.gt.3302778$$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=18059579$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16625242$$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>Durieux, B</creatorcontrib><creatorcontrib>Löffler, K</creatorcontrib><creatorcontrib>Fechtner, M</creatorcontrib><creatorcontrib>Röhl, T</creatorcontrib><creatorcontrib>Fisch, G</creatorcontrib><creatorcontrib>Dames, S</creatorcontrib><creatorcontrib>Arnold, W</creatorcontrib><creatorcontrib>Giese, K</creatorcontrib><creatorcontrib>Klippel, A</creatorcontrib><creatorcontrib>Kaufmann, J</creatorcontrib><title>RNA interference in the mouse vascular endothelium by systemic administration of siRNA-lipoplexes for cancer therapy</title><title>Gene therapy</title><addtitle>Gene Ther</addtitle><addtitle>Gene Ther</addtitle><description>RNA interference (RNAi) entails the potential for novel therapeutic strategies through the silencing of disease-causing genes
in vivo
. However, recent studies have raised an issue regarding applicable routes of administration for small interfering RNA (siRNA) molecules as therapeutics. In this study, we demonstrate that liposomally formulated siRNA molecules, the so-called siRNA-lipoplexes, but not naked siRNAs, are delivered to the tumor endothelial cells
in vivo
by microscopy. In addition, functional intracellular delivery of formulated siRNA targeting the tumor suppressor PTEN is shown in endothelial cells of the liver and tumor. Finally, the therapeutic potential of systemically administered siRNA
CD31
-lipoplexes is established by inhibition of tumor growth in two different xenograft mouse models. Our findings corroborate the applicability of this liposomal siRNA delivery technology for inducing RNAi to modulate gene expression levels in angiogenesis-dependent processes. In addition, our results advocate CD31 as a promising therapeutic target for antiangiogenic intervention. Therefore, our study provides a basis for the development of antiangiogenic cancer therapies based on RNAi.</description><subject>3T3 Cells</subject><subject>Angiogenesis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antigens, CD34 - genetics</subject><subject>Antigens, CD34 - metabolism</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Cell Biology</subject><subject>Cell differentiation, maturation, development, hematopoiesis</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>Cell physiology</subject><subject>Chemotherapy</subject><subject>Drug Administration Schedule</subject><subject>Endothelial cells</subject><subject>Endothelium</subject><subject>Endothelium, Vascular - immunology</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>Gene Silencing</subject><subject>Gene Therapy</subject><subject>Genetic aspects</subject><subject>Genetic Therapy - methods</subject><subject>Hepatocytes</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Injections, Intravenous</subject><subject>Liposomes - administration & dosage</subject><subject>Male</subject><subject>Methods</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Molecular and cellular biology</subject><subject>Nanotechnology</subject><subject>Neoplasm Transplantation</subject><subject>original-article</subject><subject>Physiological aspects</subject><subject>Platelet Endothelial Cell Adhesion Molecule-1 - genetics</subject><subject>Platelet Endothelial Cell Adhesion Molecule-1 - metabolism</subject><subject>Prostatic Neoplasms - immunology</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Prostatic Neoplasms - therapy</subject><subject>PTEN Phosphohydrolase - genetics</subject><subject>PTEN Phosphohydrolase - metabolism</subject><subject>PTEN protein</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering - administration & dosage</subject><subject>RNA-mediated interference</subject><subject>Rodents</subject><subject>siRNA</subject><subject>Therapeutic targets</subject><subject>Transplantation, Heterologous</subject><subject>Tumor suppressor genes</subject><subject>Tumors</subject><subject>Xenografts</subject><issn>0969-7128</issn><issn>1476-5462</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kt-L1DAQx4so3nr66KsEDwUfuiZpmrSPy-GPg0Ph1OeQZie7WdpmzaRy-9-bcgvrwpk8hEw-853kmymK14wuGa2aj7hbbtKyqihXqnlSLJhQsqyF5E-LBW1lWyrGm4viBeKOUipUw58XF0xKXnPBF0W6-7YifkwQHUQYLeQNSVsgQ5gQyB-DdupNJDCuQw73fhpIdyB4wASDt8SsBz96TNEkH0YSHEGfJcve78O-h3tA4kIk1mTpOAtHsz-8LJ450yO8Oq6Xxa_Pn35efy1vv3-5uV7dlrZueCrbrjKcK6sUV0YI1jjHWscUdSAtk4p3VhhODXSscp2DqlNGSdEBZ62VIKvL4upBdx_D7wkw6V2Y4phLai6FkILLqs7U2_9SrFFsHiepjelB-9GF_GQ7eLR6xZrsPcs3zdTyESrP9WxWGMH5HD9L-HCWkJkE92ljJkR98-PunH3_D7sF06cthn6ajcdzsHwAbQyIEZzeRz-YeNCM6rlpNO70Julj02T-zdGAqRtgfaKPXZKBd0cgt4PpXcy_6fHENbRua9Weno_5aNxAPDn5eOW_dP3XaA</recordid><startdate>20060901</startdate><enddate>20060901</enddate><creator>Santel, A</creator><creator>Aleku, M</creator><creator>Keil, O</creator><creator>Endruschat, J</creator><creator>Esche, V</creator><creator>Durieux, B</creator><creator>Löffler, K</creator><creator>Fechtner, M</creator><creator>Röhl, T</creator><creator>Fisch, G</creator><creator>Dames, S</creator><creator>Arnold, W</creator><creator>Giese, K</creator><creator>Klippel, A</creator><creator>Kaufmann, J</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>IQODW</scope><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>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope></search><sort><creationdate>20060901</creationdate><title>RNA interference in the mouse vascular endothelium by systemic administration of siRNA-lipoplexes for cancer therapy</title><author>Santel, A ; Aleku, M ; Keil, O ; Endruschat, J ; Esche, V ; Durieux, B ; Löffler, K ; Fechtner, M ; Röhl, T ; Fisch, G ; Dames, S ; Arnold, W ; Giese, K ; Klippel, A ; Kaufmann, J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c582t-9b3a227c7727a4418ff19f170fe6c1672bc4a20aeb13fbfe3b7a764be219c6e63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>3T3 Cells</topic><topic>Angiogenesis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antigens, CD34 - genetics</topic><topic>Antigens, CD34 - metabolism</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Care and treatment</topic><topic>Cell Biology</topic><topic>Cell differentiation, maturation, development, hematopoiesis</topic><topic>Cell Line</topic><topic>Cell Line, Tumor</topic><topic>Cell physiology</topic><topic>Chemotherapy</topic><topic>Drug Administration Schedule</topic><topic>Endothelial cells</topic><topic>Endothelium</topic><topic>Endothelium, Vascular - immunology</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression</topic><topic>Gene Silencing</topic><topic>Gene Therapy</topic><topic>Genetic aspects</topic><topic>Genetic Therapy - methods</topic><topic>Hepatocytes</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Injections, Intravenous</topic><topic>Liposomes - administration & dosage</topic><topic>Male</topic><topic>Methods</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Molecular and cellular biology</topic><topic>Nanotechnology</topic><topic>Neoplasm Transplantation</topic><topic>original-article</topic><topic>Physiological aspects</topic><topic>Platelet Endothelial Cell Adhesion Molecule-1 - genetics</topic><topic>Platelet Endothelial Cell Adhesion Molecule-1 - metabolism</topic><topic>Prostatic Neoplasms - immunology</topic><topic>Prostatic Neoplasms - metabolism</topic><topic>Prostatic Neoplasms - therapy</topic><topic>PTEN Phosphohydrolase - genetics</topic><topic>PTEN Phosphohydrolase - metabolism</topic><topic>PTEN protein</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering - 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in vivo
. However, recent studies have raised an issue regarding applicable routes of administration for small interfering RNA (siRNA) molecules as therapeutics. In this study, we demonstrate that liposomally formulated siRNA molecules, the so-called siRNA-lipoplexes, but not naked siRNAs, are delivered to the tumor endothelial cells
in vivo
by microscopy. In addition, functional intracellular delivery of formulated siRNA targeting the tumor suppressor PTEN is shown in endothelial cells of the liver and tumor. Finally, the therapeutic potential of systemically administered siRNA
CD31
-lipoplexes is established by inhibition of tumor growth in two different xenograft mouse models. Our findings corroborate the applicability of this liposomal siRNA delivery technology for inducing RNAi to modulate gene expression levels in angiogenesis-dependent processes. In addition, our results advocate CD31 as a promising therapeutic target for antiangiogenic intervention. Therefore, our study provides a basis for the development of antiangiogenic cancer therapies based on RNAi.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>16625242</pmid><doi>10.1038/sj.gt.3302778</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0969-7128 |
| ispartof | Gene therapy, 2006-09, Vol.13 (18), p.1360-1370 |
| issn | 0969-7128 1476-5462 |
| language | eng |
| recordid | cdi_proquest_journals_2644642635 |
| source | MEDLINE; SpringerLink Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | 3T3 Cells Angiogenesis Animal models Animals Antigens, CD34 - genetics Antigens, CD34 - metabolism Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Cancer therapies Care and treatment Cell Biology Cell differentiation, maturation, development, hematopoiesis Cell Line Cell Line, Tumor Cell physiology Chemotherapy Drug Administration Schedule Endothelial cells Endothelium Endothelium, Vascular - immunology Endothelium, Vascular - metabolism Fundamental and applied biological sciences. Psychology Gene Expression Gene Silencing Gene Therapy Genetic aspects Genetic Therapy - methods Hepatocytes Human Genetics Humans Injections, Intravenous Liposomes - administration & dosage Male Methods Mice Mice, Nude Molecular and cellular biology Nanotechnology Neoplasm Transplantation original-article Physiological aspects Platelet Endothelial Cell Adhesion Molecule-1 - genetics Platelet Endothelial Cell Adhesion Molecule-1 - metabolism Prostatic Neoplasms - immunology Prostatic Neoplasms - metabolism Prostatic Neoplasms - therapy PTEN Phosphohydrolase - genetics PTEN Phosphohydrolase - metabolism PTEN protein Ribonucleic acid RNA RNA Interference RNA, Small Interfering - administration & dosage RNA-mediated interference Rodents siRNA Therapeutic targets Transplantation, Heterologous Tumor suppressor genes Tumors Xenografts |
| title | RNA interference in the mouse vascular endothelium by systemic administration of siRNA-lipoplexes for cancer therapy |
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