Liudmila Vasina, Bhupendra C Reddy, Elina Sievanen, Erkki Kolehmainen and Vladimir Kral
Multifunctional Bile Acid Derivatives as Efficient RNA Transporters (Carriers)
Abstract
RNA interference (RNAi) is an emerging technology that is revolutionizing many strategic approaches to biochemical pathway analysis, drug discovery, and therapy. The siRNA can be used to suppress a specific target. Even though these molecules may have potential and strong utility function, many limitations make their clinical application difficult, including delivery problems, side effects due to off-target actions, disturbance of physiological functions of the cellular machinery involved in gene silencing, and induction of the innate immune response. This paper focus on efficient RNA transports using designed carriers, guanidine steroids. It presents the synthesis of guanidine substituted bile acids (cholic acid, deoxycholic acid and lithocholic acid) by a simple method with moderate yield. The guanidine substituted compounds are shown to be very efficient tools in generating cellular delivery vehicles as determined by in vitro studies using PAMPA (parallel artificial membrane permeability) assay.
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