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Towards gene therapy using Bifidobacterium as gene delivery system

Obiettivo

The main objective of this project is develop an efficient expression vector for Bifidobacterium, that allow the use of these bacteria as non-viral gene delivery system of prophylactic and/or therapeutic substances in the human intestine or into tumours, eliminating the bottleneck that the lack of this new innovative molecular tool is producing to underpin applications to human health using these probiotic GRAS status bacteria included in the lactic acid bacteria group. The expression vector of this project will be designed to permit an easy molecular manipulation and cloning, for the systematic study of the expression elements that can affect the expression in Bifidobacterium of proteins of prophylactic and/or therapeutic interest, allowing standardisation and characterisation in gene therapy using Bifidobacterium. These studies could elucidate which factors are important to increase the amount of protein expressed or to obtain a temporal control of the expression, crucial factors for some therapeutic applications, permitting the optimisation of the expression vector for each protein and therapeutic application. To corroborate the functionality and cell targeting versatility of the expression vector constructed in this project, and for validate the feasibility of Bifidobacterium as gene delivery system using this vector, are also objectives of this project study the therapeutic effect of the expression of two different therapeutic proteins the cytokine interleukine-10 and the angiogenic peptide endostatin, that must been expressed and delivered in two different localisation to show their therapeutic effect, gut and tumours respectively. These studies will be carried out using animal models of the human Inflammatory Bowel Disease (IBD) and tumours respectively. In the case of endostatin expression, the studies will be carried out under constitutive and radio-inducible gen promoter control.

Invito a presentare proposte

FP6-2002-MOBILITY-11
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Coordinatore

CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Contributo UE
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Indirizzo
Calle Serrano 117
MADRID
Spagna

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Costo totale
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