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RNA interference as a potential control of peste des petits ruminants

Objective

The proposal consists of a laboratory-based training project of two-years. The research and training topic concerns a new approach for the control of the pestedes petits ruminants (PPR). PPR is a highly contagious and fatal disease of small ruminants wide ly distributed in sub-Saharan Africa and the Arabian Peninsula. In spite of recognisable advantages of the vaccine developed until now, there are some limitations, which are to be overcome (poor vaccine thermal resistance and decrease of vaccine efficiency due to maternal antibody interference). Furthermore, vaccines are preventive tools that induce an immune response protecting the animals before the initial contact with the virus. Then, there is an interest to develop a curative tool that could help in th e control of the virus replication when animals are yet infected.

It was recently shown that double stranded RNA molecules (dsRNAs) promote potent and specific gene silencing in virtually all eukaryotic organisms, a phenomenon called "RNA interference" (RNA i). RNAi in mammals may be induced in basically two different ways: plasmids expressing short hairpin RNAs (shRNAs, functionally identical to siRNAs) or virus vectors (adenovirus, retrovirus) expressing shRNAs. The project goal is to achieve silencing of different PPRV genes through siRNAs and to look at the effects on the PPRV replication and protein expression in vitro and in vivo. Initially we will analyse the efficiency of shRNAs expressed from plasmids and designed for transient gene silencing in cell cultures.

Then adenoviral vector or a specific goat retroviral vector will be prepared with the efficient siRNAs and used to inhibit PPRV gene expression and replication in cell culture system. In sequence, we intend to conduct in vivo studies in goats, the natural host of PPRV. This research/training project is mainly based on laboratory-work. However, it will also provide the applicant with additional courses on animal virology, quality assurance and GLP.

Call for proposal

FP6-2002-MOBILITY-7
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CENTRE DE COOPÉRATION INTERNATIONALE EN RECHERCHE AGRONOMIQUE POUR LE DÉVELOPPEMENT
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