Characterization of carbosilane dendrimers as effective carriers of siRNA to HIV-infected lymphocytes

Journal of Controlled Release : Official Journal of the Controlled Release Society
Nick D WeberMa Angeles Muñoz-Fernandez

Abstract

One of the primary limitations of RNA interference as a technique for gene regulation is effective delivery of siRNA into the target cells. Dendrimers are nanoparticles that are increasingly being used as oligonucleotide and drug delivery vehicles. We have developed amino-terminated carbosilane dendrimers (CBS) as a means to protect and transport siRNA. Initially, stability studies showed that CBS bind siRNA via electrostatic interactions. Dendrimer-bound siRNA was found to be resistant to degradation by RNase. Cytotoxicity assays of CBS/siRNA dendriplexes with peripheral blood mononuclear cells (PBMC) and the lymphocytic cell line SupT1 revealed a maximum safe dendrimer concentration of 25 microg/ml. Next, utilizing flow cytometry and confocal microscopy, lymphocytes were seen to be successfully transfected by fluorochrome-labeled siRNA either naked or complexed with CBS. Dendriplexes with +/- charge ratio of 2 were determined to have the highest transfection efficiency while maintaining a low level of toxicity in these systems including hard-to-transfect HIV-infected PBMC. Finally, CBS/siRNA dendriplexes were shown to silence GAPDH expression and reduce HIV replication in SupT1 and PBMC. These results point to the possibility...Continue Reading

References

Mar 10, 2001·Genes & Development·P A Sharp
Aug 18, 2001·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·E Imai
Jun 4, 2002·Nature Medicine·Carl D NovinaPhillip A Sharp
Jul 2, 2002·Nature Medicine·Roger J Pomerantz
Jan 15, 2003·Journal of Virology·Deborah PersaudRobert F Siliciano
Mar 26, 2003·The Journal of Antimicrobial Chemotherapy·Glen A Coburn, Bryan R Cullen
Apr 8, 2003·Current Medicinal Chemistry·Aaron HirkoJeffrey A Hughes
Apr 8, 2003·Current Medicinal Chemistry·Dan Niculescu-DuvazCaroline J Springer
Jun 5, 2003·Nature Reviews. Molecular Cell Biology·Derek M DykxhoornPhillip A Sharp
Feb 14, 2004·Journal of Virology·Atze T DasBen Berkhout
Mar 11, 2005·Advanced Drug Delivery Reviews·Ram I Mahato
May 24, 2005·Nature Biotechnology·Erwei SongJudy Lieberman
Nov 22, 2005·Advanced Drug Delivery Reviews·Ruth Duncan, Lorella Izzo
Nov 25, 2005·Advanced Drug Delivery Reviews·Sönke Svenson, Donald A Tomalia
Nov 29, 2005·Advanced Drug Delivery Reviews·Christine DufèsAndreas G Schätzlein
Apr 11, 2006·Journal of Immunological Methods·Jiyi YinTerri H Finkel
Dec 13, 2006·Journal of Controlled Release : Official Journal of the Controlled Release Society·Leto-Aikaterini TzivelekaConstantinos M Paleos
Jan 16, 2007·Molecular Pharmaceutics·Constantinos M PaleosZili Sideratou
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Dan PeerMotomu Shimaoka
Mar 22, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Inge S ZuhornDick Hoekstra
Jun 23, 2007·Biomacromolecules·Dzmitry ShcharbinMa Angeles Muñoz-Fernandez
Oct 5, 2007·Journal of Controlled Release : Official Journal of the Controlled Release Society·Baichao MaHongtao Lv
Nov 21, 2007·Journal of Controlled Release : Official Journal of the Controlled Release Society·Oliver GermershausThomas Kissel
Mar 19, 2008·Nucleic Acids Research·Ying Poi LiuPavlina Konstantinova
Mar 21, 2008·Expert Opinion on Biological Therapy·Sunit K Singh

❮ Previous
Next ❯

Citations

Jun 4, 2013·Biomaterials·Abhijit A Date, Christopher J Destache
Jul 8, 2011·Accounts of Chemical Research·Xiaowei MaXing-Jie Liang
Oct 26, 2011·Molecular Pharmaceutics·Rafael GrasLuís A López-Fernández
Sep 29, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jiehua ZhouJohn J Rossi
Nov 18, 2009·Biochemistry. Biokhimii︠a︡·D G ShcharbinM Bryszewska
Oct 20, 2010·International Journal of Nanomedicine·Rama Mallipeddi, Lisa Cencia Rohan
Aug 28, 2010·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Jose Luis JiménezMaría Angeles Muñoz-Fernández
Feb 13, 2010·Nanomedicine·Tewodros MamoOmid C Farokhzad
Nov 3, 2010·Nanomedicine·Inmaculada PosadasValentín Ceña
Dec 1, 2010·Therapeutic Delivery·Olivia M MerkelThomas Kissel
Nov 30, 2013·TheScientificWorldJournal·Jiangyu WuZiying He
Apr 12, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ana Judith Perisé-BarriosMaría Ángeles Muñoz-Fernandez
May 8, 2014·Journal of Materials Science. Materials in Medicine·Antos ShakhbazauRajiv Midha
Jul 26, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jianqing PengXiangbo Li
May 17, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Laura M EnsignJustin Hanes
Jan 7, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ma Jesús SerramíaMa Ángeles Muñoz-Fernández
Jun 2, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·L ChoncoM A Muñoz-Fernández
Mar 2, 2012·Biomaterials·Rafael GrasM Angeles Muñoz-Fernández
Sep 21, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Nick D WeberMaría Ángeles Muñoz-Fernández
May 7, 2015·Chemical Reviews·Jiepin YangYiyun Cheng
Nov 28, 2009·Bioorganic & Medicinal Chemistry·Alexandra Pérez-AnesIsabelle Rico-Lattes
Oct 10, 2009·Journal of Controlled Release : Official Journal of the Controlled Release Society·Dzmitry ShcharbinMaria Bryszewska
Mar 5, 2016·Chemical Society Reviews·Anne-Marie Caminade
Sep 23, 2009·International Journal of Pharmaceutics·Antos ShakhbazauMaria Bryszewska
Aug 26, 2009·Bioorganic Chemistry·V Biricova, A Laznickova
Apr 1, 2009·Journal of Controlled Release : Official Journal of the Controlled Release Society·Dzmitry ShcharbinMaria Bryszewska
Nov 3, 2015·Molecular Pharmaceutics·Simeon K Adesina, Emmanuel O Akala
Feb 16, 2011·Macromolecular Bioscience·Hamidreza Montazeri AliabadiHasan Uludağ
Jul 5, 2012·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Joanna LazniewskaTeresa Gabryelak
Sep 23, 2010·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Peter S Kim, Sarah W Read
Apr 11, 2015·Advanced Drug Delivery Reviews·Sophia G Antimisiaris, Spyridon Mourtas
Aug 13, 2014·Advanced Healthcare Materials·Nathaly SegoviaNatalie Artzi
May 12, 2012·Biochimica Et Biophysica Acta·Maksim IonovMaria Bryszewska
Mar 23, 2015·International Journal of Pharmaceutics·Volha DzmitrukMaria Bryszewska
Mar 5, 2015·International Journal of Pharmaceutics·Katarzyna MilowskaMaria Bryszewska
Dec 31, 2010·Colloids and Surfaces. B, Biointerfaces·Elzbieta Pedziwiatr-WerbickaMaria Bryszewska
Mar 21, 2015·International Journal of Pharmaceutics·Maksim IonovMaria Bryszewska
Feb 24, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Olivia M MerkelThomas Kissel
Jul 17, 2012·Biomaterials·Prashant KesharwaniNarendra Kumar Jain
Oct 5, 2014·Drug Discovery Today·Vijay MishraNarendra K Jain

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.