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Influence of lipoplex surface charge on siRNA delivery: application to the in vitro downregulation of CXCR4 HIV-1 co-receptor.
MedLine Citation:
PMID:  23289797     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Carole Lavigne; Kathryn Slater; Niranjala Gajanayaka; Christian Duguay; Erika Arnau Peyrotte; Germaine Fortier; Martin Simard; Arnold J Kell; Michael L Barnes; Alain R Thierry
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-7
Journal Detail:
Title:  Expert opinion on biological therapy     Volume:  -     ISSN:  1744-7682     ISO Abbreviation:  Expert Opin Biol Ther     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101125414     Medline TA:  Expert Opin Biol Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
National HIV & Retrovirology Laboratories, National Microbiology Laboratory, Public Health Agency of Canada , 200 Tunney's Pasture Driveway, Ottawa, Ontario K1A 0K9 , Canada +1 613 941 8857 ; +1 613 948 4026 ; carole.lavigne@phac-aspc.gc.ca.
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