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Development of a proof of principle model for the therapeutical use of induced P...

Development of a proof of principle model for the therapeutical use of induced Pluripotent Stem iPS cells "Cystic Fibrosis is a hereditary disease produced by the absence or malfunctioning of the Cystic Fibrosis Transmembrane Conductase Regulator (CFTR) gene. To date over 1,200 alterations in the DNA composition of the CFTR gene have... ver más

19/07/2013

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231K€

Presupuesto del proyecto: 231K€

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FUNDACIO INSTITUT D' INVESTIGACIO SANITARIA I... Otra investigación y desarrollo experimental en ciencias naturales y técnicas asociacion

TRL 4-5 | 50K€

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Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2013-07-19 No tenemos la información de la convocatoria

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Líder del proyecto

FUNDACIO INSTITUT D' INVESTIGACIO SANITARIA I... Otra investigación y desarrollo experimental en ciencias naturales y técnicas asociacion

TRL 4-5 | 50K€

Presupuesto del proyecto 231K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto "Cystic Fibrosis is a hereditary disease produced by the absence or malfunctioning of the Cystic Fibrosis Transmembrane Conductase Regulator (CFTR) gene. To date over 1,200 alterations in the DNA composition of the CFTR gene have been detected, although the deletion of the phenylalanine in position 508 (ΔF508) is responsible for more than 70% of the cases described in the European Population. CF is a degenerative disease, which can be considered as the main genetic cause of death in Caucasian children. Its first manifestations occur in early childhood, generally affecting the respiratory tract, and later extending to other organs. The identification and isolation of the gene responsible for the disease raised great expectations of finding a treatment. However, such hopes have yet to be realized. Different attempts to develop effective gene therapy protocols have not provided satisfactory results. In the current circumstances, I believe that the best strategy to develop an effective treatment for CF is to use autologous grafts of healthy lung epithelium progenitors, derived, in vitro, from human induced pluripotent stem (iPS) cells. The method that I propose will be developed simultaneously in human and mouse cells, and includes the following steps: (I) Production of iPS cells from keratinocytes obtained from ΔF508 CF patients and ΔF508 mutant mice; (II) Correction of the mutation in the iPS cells; (III) in vitro differentiation of repaired iPS (iPSr) cells up to a state compatible with their functional integration into the pulmonary epithelium; (IV) Transplantation of the differentiated cells into suitable receptors. Steps I through III will be carried out in parallel with human and mouse cells. Step IV will serve as a preclinical study and will be performed only in mice. During the process we plan to: 1) incorporate new, less aggressive de-differentiation methods, 2) improve homologous recombination efficiency in iPS cells, 3) determine the optimal differ"

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