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

Hepatitis 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 fa...

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Bibliographic Details
Published in:Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2017, Vol.5 (4), p.858-865
Main Authors: Crouchet, E, Saad, R, Affolter-Zbaraszczuk, C, Ogier, J, Baumert, T F, Schuster, C, Meyer, F
Format: Article
Language:English
Subjects:
Calcium phosphate
Chemical Sciences
Coating
Gene therapy
Hepatitis C virus
Human health and pathology
Infectious diseases
Life Sciences
Mathematical models
Medicinal Chemistry
Nanoparticles
Nanostructure
Ribonucleic acids
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Summary:Hepatitis 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 (πPEI). 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.
ISSN:2050-750X
2050-7518
DOI:10.1039/c6tb01718e