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Accelerating Research & Development for Advanced Therapies

Descripción del proyecto

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Mejorar la eficacia del vector de virus adenoasociados en la terapia génica

Los virus adenoasociados (VAA) son un tipo de virus no encapsulado que pueden modificarse para administrar ADN de interés a células objetivo con fines terapéuticos. Sin embargo, la inmunidad preexistente convierte los vectores de VAA en una opción ineficaz, dado que el hospedador los elimina. El proyecto ARDAT, financiado con fondos europeos, reúne a expertos del ámbito de la terapia génica para colmar las brechas del conocimiento relativas a la inmunogenicidad de los vectores de VAA en aplicaciones de terapia génica. Además, los socios estudiarán el metabolismo de los vectores de VAA para terapia génica, su tasa de degradación y su capacidad para perdurar en su forma episomal. La visión a largo plazo de ARDAT consiste en mejorar la eficacia de los vectores de VAA en los ensayos de terapia génica.

Objetivo

Major current hurdles for wide clinical use of AAV vectors are attributable primarily to: (i) host elimination by both immune and non-immune sequestering mechanisms – such neutralization by host antibody responses critically limits the possibility of repeated AAV delivery; (ii) AAVs are prevalent in the environment and hence a large proportion of the population carry AAV antibodies (up to 80%)– this pre-existing immunity renders AAV unable to infect target cells forcing substantial patient cohorts to be excluded from clinical trials.
The current proposal is founded on compelling track record in the field and brings together a ‘best-with-best’ multidisciplinary team of international leading academic and EFPIA partners with complimentary expertise in gene therapy, immunology, chemistry, engineering, biotechnology, drug safety, viral vector production, regulatory and clinical trials. The overall goal is to analyse the currently available clinical data and then design preclinical and clinical studies to fill the knowledge gaps in advanced therapies development. Our main aims are to: 1) Develop improved model systems for predicting product immunogenicity in humans. This will be achieved by generating human and NHP 3D hepatic models; 2) Enhance our understanding of gene/cell therapy drug metabolism inside a host of cell types. The plan is to define metabolism of the therapeutic vector genome in different cell types to understand whether rates of degradation, episomal maintenance, or integration, and metabolic stress induced by AAV vector transgene expression vary from cell to cell. We will then adopt strategies to mitigate the loss of vector genomes and improve persistence; 3) Use diverse clinical expertise to establish the clinical factors around pre-existing immunity limiting patient access to advanced therapies therapy; 4) Engage regulators to ensure that the concepts and the data generated through this IMI programme will fill the gaps and support furture trials.

Ámbito científico

Palabras clave

Programa(s)

Tema(s)

Convocatoria de propuestas

H2020-JTI-IMI2-2019-18-two-stage

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Régimen de financiación

RIA - Research and Innovation action

Coordinador

THE UNIVERSITY OF SHEFFIELD
Aportación neta de la UEn
€ 2 699 812,25
Dirección
FIRTH COURT WESTERN BANK
S10 2TN Sheffield
Reino Unido

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Región
Yorkshire and the Humber South Yorkshire Sheffield
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
€ 3 469 812,25

Participantes (33)

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Última actualización: 22 Abril 2024

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Permalink: https://cordis.europa.eu/project/id/945473/es

European Union, 2024