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Novel Strategies for the Modulation of Immunity to AAV vectors

Adeno-associated virus (AAV) vectors are among the most efficient vectors for in vivo gene transfer. Experience in human gene transfer trials showed that targeting hepatocytes with AAV vectors has the potential to correct diseases... ver más

30/04/2017

UNIVERSITE PIERRE...

100K€

Presupuesto del proyecto: 100K€

Líder del proyecto

UNIVERSITE PIERRE ET MARIE CURIE No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2017-04-30 No tenemos la información de la convocatoria

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UNIVERSITE PIERRE ET MARIE C...

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Líder del proyecto

UNIVERSITE PIERRE ET MARIE CURIE No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 100K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Adeno-associated virus (AAV) vectors are among the most efficient vectors for in vivo gene transfer. Experience in human gene transfer trials showed that targeting hepatocytes with AAV vectors has the potential to correct diseases like hemophilia, congenital blindness, and lipoprotein lipase deficiency. However, these studies also suggest that one of the last obstacles to be overcome in order to achieve long-term disease correction is the immune system. As a result of exposure to wild type AAV, a significant portion of the human population will develop both humoral and cellular immunity to the virus, which can greatly affect the safety and efficacy of gene transfer with recombinant AAV vectors. This proposal combines knowledge on immunology and AAV vector mediated gene transfer, with the ultimate goal of developing safe and effective gene therapy protocols. Studies in humans undergoing AAV gene transfer will help identify markers of T cell activation and correlate them with the outcome of gene transfer. Studies in humans receiving immunosuppressive (IS) regimens will help identifying drug regimens that could be safely used to modulate B and T cell immunity to AAV in the context of gene transfer. In the third aim of this proposal, IS regimens will be tested in vivo in the relevant animal models. Results from these studies will contribute to design safe and effective clinical gene transfer studies by providing new tools and markers for safety assessment and early intervention aimed at modulating detrimental immune responses directed against the AAV vector capsid. Furthermore, these studies address the issue of humoral immunity to AAV by identifying strategies to overcome the limitation of anti-AAV antibodies, thus allowing for treatment of a significant proportion of humans otherwise non eligible for enrollment in gene transfer trials.

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