Name of Fellow


RUI JORGE GONÇALVES PEREIRA NOBRE

Institution


Funder


FCT

Contact information of fellow


Country


Portugal

Title of project/programme


SILENCING MACHADO-JOSEPH DISEASE THROUGH THE SYSTEMIC ROUTE

Source of funding information


FCT

Total sum awarded (Euro)


€ 116,640

Start date of award


01/01/10

Total duration of award in years


6.0

The project/programme is most relevant to:


Spinocerebellar ataxia (SCA)

Keywords


Research Abstract


Our group has recently showed that allele-specific silencing of ataxin-3 significantly decreased the severity of the neuropathological abnormalities in a rat model of Machado-Joseph disease (MJD) upon intracranial injection of lentiviral vectors (Alves et al., 2008a). Although intracranial injection is a safe procedure there is a need for a less invasive system. The aim of this project is to develop a system that will allow delivery of siRNA-based treatments to the brain by a vascular route. AAV9 vectors will be engineered to transduce neurons of the adult mouse. Silencing sequences, previously shown to efficiently abrogate MJD, will be cloned into AAV9 and its efficacy evaluated in animal models (Alves et al., 2008b). It is expected that this project will enable the development of a new gene delivery system for the treatment of MJD and constitute a proof of principle for systemic gene therapy of a wide range of neurodegenerative diseases.

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