Influence of lipoplex surface charge on siRNA delivery: application to the in vitro downregulation of CXCR4 HIV-1 co-receptor

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DOIResolve DOI: http://doi.org/10.1517/14712598.2013.743526
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TypeArticle
Journal titleExpert Opinion on Biological Therapy
ISSN1471-2598
Volume13
Issue7
Pages973985; # of pages: 13
Subjectanti-HIV therapy, CXCR4, lipoplex charge, nanodelivery system, Neutraplex, siRNA delivery
AbstractObjective: Cationic lipidic formulations have been successfully used to deliver small interfering RNA (siRNA) into cells but they show limitations for in vivo application due to their cytotoxicity and instability in the presence of serum. To overcome these limitations, the authors developed an anionic lipid-based carrier named Neutraplex (Nx). Here, they wanted to investigate the influence of the lipoplex (Lx) surface charge on cytotoxicity, delivery and silencing activity of siRNAs. Methods: The efficiency of three Nx formulations (cationic, close to neutrality and anionic) to deliver anti-CXCR4 siRNAs in MAGI cells was investigated and compared with the cationic commercial transfection reagent Lipofectamine RNAiMAX. Cellular uptake and intracellular localization of a fluorescent siRNA was monitored in live cells using fluorescence microscopy and silencing activity was measured by flow cytometry and RT-PCR analysis. Results: The authors found that the Lx surface charge influenced cellular uptake and silencing activity of siRNA in cell cultures. Although cationic Lx formulations were the most efficient carriers to deliver active silencing siRNAs, negatively charged lipoplexes were taken up by cells, delivered active siRNAs and presented low cytotoxicity. Conclusions: Altogether, the findings support further investigation for in vivo delivery of therapeutic siRNAs using Nx. Furthermore, this study indicates that anionic delivery systems may have potential for in vivo RNAi therapeutics.
Publication date
LanguageEnglish
AffiliationSecurity and Disruptive Technologies; National Research Council Canada
Peer reviewedYes
NPARC number21270426
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Record identifierfe44888f-f9c7-478a-be32-92890ad06f90
Record created2014-02-10
Record modified2016-05-09
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