Composite vector formulation for multiple siRNA delivery as a host targeting antiviral in a cell culture model of hepatitis C virus (HCV) infection

Abstract

bceHepatitis C virus (HCV) infection is a major cause of chronic liver disease and cancer worldwide. RNA interference (RNAi)-based gene therapies have emerged recently as a promising tool to treat chronic viral infections. Indeed, small interfering RNAs (siRNAs) provide an opportunity to target host factors required for the viral life cycle. In this study, we evaluated a novel nanovector-based approach for siRNA delivery in a model of chronically infected hepatic cells. We designed original composite nanoparticles by coating the calcium phosphate core with siRNAs targeting HCV host-factors and pyridylthiourea-grafted polyethyleneimine (pPEI). Using combinations of different siRNAs, we observed an efficient and prolonged decrease of HCV replication. Moreover, we showed that the layer-by-layer technique of coating applied to our nanoparticles triggers a sequential release of siRNAs acting on different steps of the HCV life cycle.Together, our results demonstrate the efficacy of these nanoparticles for siRNA delivery and open new perspectives for antiviral therapies.

Delivery of Inorganic Polyphosphate into Cells Using Amphipathic Oligocarbonate Transporters

“…Nuclear localization is suggestive of one of polyP’s hypothesized functions of affecting gene expression by disrupting nucleohistone complexes . This distribution is particularly interesting, in this case, because it is in stark contrast with other FITC-labeled anions such as siRNA which tend to show only cytosolic fluorescence and exclude the nucleus. ,, …”

“…53 This distribution is particularly interesting, in this case, because it is in stark contrast with other FITC-labeled anions such as siRNA which tend to show only cytosolic fluorescence and exclude the nucleus. 30 , 54 , 55 …”

“…53 This distribution is particularly interesting, in this case, because it is in stark contrast with other FITClabeled anions such as siRNA which tend to show only cytosolic fluorescence and exclude the nucleus. 30,54,55 Protection of PolyP from Phosphatase Degradation. An effective drug delivery technology should protect its cargo from the extracellular environment and/or during circulation prior to intracellular delivery.…”