RNA interference in the mouse vascular endothelium by systemic administration of siRNA-lipoplexes for cancer therapy

Gene Therapy
A SantelJ Kaufmann

Abstract

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.

References

Jun 17, 1992·Journal of the National Cancer Institute·R A StephensonI J Fidler
Jan 3, 1991·The New England Journal of Medicine·N WeidnerJ Folkman
Jan 1, 1995·Annals of Oncology : Official Journal of the European Society for Medical Oncology·P B VermeulenL Y Dirix
Apr 29, 1998·The Journal of Clinical Investigation·G ThurstonD M McDonald
Oct 3, 2002·Nature Reviews. Cancer·Robert Kerbel, Judah Folkman
May 29, 2003·Nucleic Acids Research·Frank CzaudernaJörg Kaufmann
Jun 5, 2003·Nature Reviews. Molecular Cell Biology·Derek M DykxhoornPhillip A Sharp
Jun 5, 2003·Nature Medicine·Napoleone FerraraJennifer LeCouter
Oct 2, 2003·Current Opinion in Cell Biology·Neta Ilan, Joseph A Madri
Oct 25, 2003·Nucleic Acids Research·Frank CzaudernaJörg Kaufmann
Jun 3, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yun ZhangWilliam M Pardridge
Jul 30, 2004·The EMBO Journal·Frauke LeendersAnke Klippel
Sep 18, 2004·Cancer Gene Therapy·Tie-gang LiuRong-guang Shao
Nov 3, 2004·Nucleic Acids Research·Raymond M SchiffelersMartin C Woodle
Nov 26, 2004·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Stephen B Fox, Adrian L Harris
Dec 1, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Junichi YanoTatsuro Irimura
Apr 2, 2005·Cancer Gene Therapy·Qixin Leng, Archibald James Mixson
May 14, 2005·Cancer Gene Therapy·Tom C Karagiannis, Assam El-Osta
May 24, 2005·Nature Biotechnology·Erwei SongJudy Lieberman
Aug 24, 2005·FEBS Letters·Susan L Uprichard
Sep 30, 2005·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Karine BollérotThierry Jaffredo
Oct 1, 2005·Leukemia & Lymphoma·Carmen BergomPeter J Newman
Nov 5, 2005·Nature Clinical Practice. Oncology·Giampietro GaspariniNapoleone Ferrara

❮ Previous
Next ❯

Citations

Apr 26, 2007·Applied Microbiology and Biotechnology·Achim Aigner
Sep 21, 2013·Journal of Medicinal Chemistry·Sara FalsiniAnnarosa Arcangeli
May 5, 2012·Cancer Gene Therapy·H ShenM Ferrari
Oct 13, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kevin J PolachAnke Geick
Dec 22, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Garrett R Rettig, Mark A Behlke
Jan 25, 2013·Molecular Therapy. Nucleic Acids·Dirk Haussecker
Jan 1, 2012·Molecular Therapy. Nucleic Acids·James C GeogheganBeverly L Davidson
Jan 11, 2012·Nucleic Acid Therapeutics·Frank J HernandezJames O McNamara
Nov 26, 2008·Oligonucleotides·Mark A Behlke
May 16, 2009·Oligonucleotides·Marjorie RobbinsIan MacLachlan
Jun 19, 2008·Nucleic Acids Research·Rudy JulianoHyumin Kang
Jun 6, 2009·Pigment Cell & Melanoma Research·Melissa A TranGavin P Robertson
Feb 21, 2009·The Journal of Clinical Investigation·Adam D JudgeIan MacLachlan
Sep 17, 2009·The AAPS Journal·Sherry Y Wu, Nigel A J McMillan
Oct 6, 2007·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yuki TakahashiYoshinobu Takakura
Sep 17, 2009·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Marta López-FragaAna Jiménez
Apr 24, 2012·ISRN Oncology·Olivia SimmonsJohn Nemunaitis
Mar 19, 2013·Trends in Molecular Medicine·Jianfeng GuoCaitriona M O'Driscoll
Jul 28, 2012·Therapeutic Delivery·Shaguna SethMichael V Templin
Nov 14, 2013·Cellular and Molecular Life Sciences : CMLS·Lígia Catarina Gomes-da-SilvaJoão Nuno Moreira
Jan 7, 2014·Molecular Therapy : the Journal of the American Society of Gene Therapy·V FehringJörg Kaufmann
Jul 8, 2014·Therapeutic Delivery·Andrew D Miller
Jul 16, 2014·Nature Reviews. Genetics·Hao YinDaniel G Anderson
May 13, 2014·Nature Nanotechnology·James E DahlmanDaniel G Anderson
Jul 12, 2013·BioMed Research International·Jong-Min LeeYoung-Seok Cho
May 11, 2011·World Journal of Surgery·John NemunaitisF Charles Brunicardi
Nov 8, 2013·Expert Review of Medical Devices·Andrew D Miller
Apr 28, 2009·Expert Opinion on Biological Therapy·Leiming Li, Yu Shen
Aug 2, 2007·Expert Opinion on Biological Therapy·Fritz Eckstein
Feb 15, 2011·Expert Opinion on Drug Delivery·Ezharul Hoque Chowdhury
Jul 23, 2015·Expert Opinion on Biological Therapy·Manuele GoriAlberto Rainer
Sep 7, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Oscar HaighMark A F Kendall
Dec 10, 2015·IET Nanobiotechnology·Neha Mehrotra, Ravi Mani Tripathi
Jan 8, 2016·Journal of the American Chemical Society·Mark W TibbittRobert Langer
Jun 26, 2012·Current Opinion in Pharmacology·Christopher AlabiDaniel Anderson
Nov 15, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Nahum AllonBhupendra P Doctor
Oct 25, 2011·Cellular Signalling·Ma Eugenia DíazDaniel Turyn
Sep 23, 2014·Journal of Proteome Research·Huiqin ZhuoYongxiang Zhao
Apr 19, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Anne SchlegelVirginie Escriou
Dec 16, 2010·Advanced Drug Delivery Reviews·Feng Li, Ram I Mahato
Feb 11, 2010·Microvascular Research·Jörg KaufmannAnsgar Santel
Sep 5, 2009·Biotechnology Advances·Saba KhaliqSajida Hassan

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.