DOI | Resolve DOI: https://doi.org/10.1517/14712598.2013.743526 |
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Author | Search for: Lavigne, Carole; Search for: Slater, Kathryn; Search for: Gajanayaka, Niranjala; Search for: Duguay, Christian; Search for: Arnau Peyrotte, Erika; Search for: Fortier, Germaine; Search for: Simard, Martin; Search for: Kell, Arnold J.1; Search for: Barnes, Michael L.1; Search for: Thierry, Alain R. |
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Affiliation | - National Research Council of Canada. Security and Disruptive Technologies
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Format | Text, Article |
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Subject | anti-HIV therapy, CXCR4, lipoplex charge, nanodelivery system, Neutraplex, siRNA delivery |
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Abstract | Objective: 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. |
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Publication date | 2013-07 |
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In | |
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Language | English |
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Peer reviewed | Yes |
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NPARC number | 21270426 |
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Export citation | Export as RIS |
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Report a correction | Report a correction (opens in a new tab) |
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Record identifier | fe44888f-f9c7-478a-be32-92890ad06f90 |
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Record created | 2014-02-10 |
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Record modified | 2020-04-22 |
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