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Accelerating Research & Development for Advanced Therapies

Descrizione del progetto

DE EN ES FR IT PL

Migliorare l’efficienza del vettore di terapia genica AAV

Il virus adeno-associato (AAV) è un virus privo di pericapside che può essere manipolato per fornire DNA di interesse alle cellule bersaglio per scopi di terapia genica. Tuttavia, l’immunità preesistente rende i vettori AAV inefficienti poiché vengono eliminati dall’ospite. Il progetto ARDAT, finanziato dall’UE, unisce esperti in materia di terapia genica per colmare le lacune di conoscenza riguardo all’immunogenicità dei vettori AAV nelle applicazioni di terapia genica. Inoltre, partner studieranno il metabolismo dei vettori di terapia genica AAV, il loro tasso di decomposizione e la loro capacità di permanenza in forma episomale. La visione sul lungo periodo di ARDAT è il miglioramento dell’efficienza del vettore AAV negli studi di terapia genica.

Obiettivo

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.

Campo scientifico

Parole chiave

Programma(i)

Argomento(i)

Invito a presentare proposte

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

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Meccanismo di finanziamento

RIA - Research and Innovation action

Coordinatore

THE UNIVERSITY OF SHEFFIELD
Contribution nette de l'UE
€ 2 699 812,25
Indirizzo
FIRTH COURT WESTERN BANK
S10 2TN Sheffield
Regno Unito

Mostra sulla mappa
Regione
Yorkshire and the Humber South Yorkshire Sheffield
Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 3 469 812,25

Partecipanti (33)

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Ultimo aggiornamento: 22 Aprile 2024

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

European Union, 2024