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Accelerating Research & Development for Advanced Therapies

Description du projet

Améliorer l’efficacité des vecteurs de thérapie génique VAA

Les virus adéno-associés (VAA) sont des virus non enveloppés qui peuvent être modifiés pour acheminer de l’ADN d’intérêt utile à des cellules cibles à des fins de thérapie génique. Une immunité préexistante rend toutefois les vecteurs VAA inefficaces car ils sont éliminés de l’hôte. Le projet ARDAT, financé par l’UE, rassemble des experts du domaine de la thérapie génique en vue de combler les lacunes dans nos connaissances sur l’immunogénicité des vecteurs VAA, en ce qui concerne les applications de thérapie génique. Par ailleurs, les partenaires étudieront le métabolisme des vecteurs de thérapie génique VAA, leur taux de dégradation et leur capacité à persister sous forme épisomale. La vision à long terme d’ARDAT consiste à améliorer l’efficacité des vecteurs VAA dans les essais de thérapie génique.


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.


Contribution nette de l'UE
€ 2 699 812,25
S10 2TN Sheffield

Voir sur la carte

Yorkshire and the Humber South Yorkshire Sheffield
Type d’activité
Higher or Secondary Education Establishments
Coût total
€ 3 469 812,25

Participants (33)