Abstract
Small interference RNA (siRNA) is an important research tool, and also has the potential for clinical application. RNA interference (RNAi) approaches allow degradation of selective mRNA coding for pathogenic or disease-related proteins. RNAi pathway can be taken advantage of by the delivery of chemically synthesized siRNA. To fully attain its potential a sufficient siRNA must be delivered to the cell's cytoplasm. Cellular delivery of polyanions such as siRNA, while a challenging problem, may be addressed by the use of cationic macromolecules, the two major classes being lipids and polymers. In this study we compared two model cationic vectors liposomes (lipoplexes) and polyethelyenimine (PEI) (polyplexes). Complexes of the cationic macromolecules and siRNA did not differ in terms of their cellular uptake as determined by flow cytometry. However, it was demonstrated that the lipoplexes decomplexed more easily than the polyplexes. Differences in the biological activity of the siRNA were observed using commercially available siTOX siRNA. Lipoplexes resulted in dose-dependent siRNA activity; to 76.4 +/- 5.9% cell death was seen 48 hours posttransfection using 80 nmol siTOX. In summary, the selection of delivery vector can have a profound impact on biological activity of siRNA molecules. siRNA decomplexation from the cationic vector might be an important factor in the future development of new vectors.
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