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MITCARE

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Mitochondrial Medicine developing treatments of OXPHOS defects in recombinant m...

Mitochondrial Medicine developing treatments of OXPHOS defects in recombinant mammalian models. Mitochondria are the major source of ATP, synthesized by the mitochondrial respiratory chain (MRC) through the process of oxidative phosphorylation. ATP deficiency leads to cellular dysfunction and ultimately death. In mammals, 13... ver más

31/12/2018

THE CHANCELLOR MAS...

3M€

Presupuesto del proyecto: 3M€

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THE CHANCELLOR MASTERS AND SCHOLARS OF THE UN... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

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Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2018-12-31 No tenemos la información de la convocatoria

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THE CHANCELLOR MASTERS AND S...

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FINCB

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NC3Rs

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Líder del proyecto

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UN... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 3M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Mitochondria are the major source of ATP, synthesized by the mitochondrial respiratory chain (MRC) through the process of oxidative phosphorylation. ATP deficiency leads to cellular dysfunction and ultimately death. In mammals, 13 mitochondrial DNA (mtDNA)-encoded subunits interact with over 70 nuclear-encoded subunits to form four of the five MRC complexes. Many additional factors are essential for the regulation of MRC activity, and the maintenance and expression of mtDNA. As a result, genetic defects affecting either genome can compromise ATP synthesis and cause human disease. There is no effective treatment for mitochondrial disorders. Major hurdles to this achievement include (i) the still incomplete molecular definition of mitochondrial disease; (ii) the poorly understood function of many disease gene products, (iii) the difficulty to rationally manipulate the complex biochemical and genetic systems underpinning mitochondrial bioenergetics. The ultimate scope of MitCare is to develop effective therapy in mitochondrial medicine. MitCare will implement three Workpackages (WP). WP1 will test the effects of pharmacological stimulation of mitochondrial biogenesis in mouse disease models. WP2 will test the effects of Adeno-Associated Viral (AAV)- and lentiviral-mediated delivery of therapeutic genes, in mouse models and human mutant cells, respectively. Since the clinical features of human disorders often fail to be faithfully replicated in mice, WP3 will implement the creation of a mitochondrial disease model in the pig, whose proximity to humans is much closer than mice. The Surf1 gene, encoding an assembly factor of complex IV, will be disrupted by zincfinger nuclease technology in swine fibroblasts, which will then serve to clone a Surf1 knockout pig by somatic cell nuclear transfer. Mitopigs will be used to test the direct transferability of experimental treatments from suitable mammalian models to the clinics.

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