RETGENTX

Overcoming the challenge of large gene transfer for the therapy of inherited retinal diseases

Coordinatore	FONDAZIONE TELETHON    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Italy [IT]
Totale costo	1˙500˙000 €
EC contributo	1˙500˙000 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2011-StG_20101109
Funding Scheme	ERC-SG
Anno di inizio	2012
Periodo (anno-mese-giorno)	2012-01-01   -   2016-12-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	FONDAZIONE TELETHON  Organization address address: VIA VARESE 16/B city: ROMA postcode: 185 contact info Titolo: Ms. Nome: Irene Cognome: Mearelli Email: send email Telefono: 3906440151 Fax: 390644000000	IT (ROMA)	hostInstitution	1˙500˙000.00
2	FONDAZIONE TELETHON  Organization address address: VIA VARESE 16/B city: ROMA postcode: 185 contact info Titolo: Prof. Nome: Alberto Cognome: Auricchio Email: send email Telefono: 390816000000 Fax: 390816000000	IT (ROMA)	hostInstitution	1˙500˙000.00

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 Obiettivo del progetto (Objective)

'Inherited retinal diseases (IRDs) cause blindness in over 200,000 individuals in Europe. The majority are due to mutations in genes expressed in photoreceptors (PR) in the retina. We have recently demonstrated the safety and efficacy of gene therapy for IRDs in patients with Leber congenital amaurosis (LCA). One of the major limitations to extend this clinical success to other blinding conditions is that many are caused by mutations in genes with large coding sequences that exceed the cargo capacity of the most efficient gene transfer vector for PR, the adeno-associated virus (AAV). Conversely, vectors for large gene delivery like lentiviral (LV) or high-capacity adenoviral (HC-Ad) vectors have poor PR tropism. This project aims at overcoming the challenge of large gene delivery to the retina. We propose to either expand AAV cargo capacity or to identify/modify LV and HD-Ad vectors with improved PR transduction ability. We plan to expand AAV cargo capacity by either producing AAV vectors from single plasmid containing large genes or by generating 2-split AAV vectors each containing one of 2 halves of a large gene which is reconstituted upon AAV intermolecular concatemerization in the nucleus of target cells. In parallel, we will screen a series of existing LV pseudotypes and Ad serotypes for their ability to transduce PR. Alternatively, we propose to modify the Ad capsid or LV envelope using epitopes identified by in vivo biopanning that bind to PR and. We will compare the efficiency of the three vector platforms to transduce murine and porcine PR. The platform with highest PR transduction efficiency will then be used to correct the retinal phenotype of murine models of common severe IRDs due to mutations in large genes. Overcoming the challenge of large gene transfer will allow to cure photoreceptor-specific diseases which are currently untreatable and will provide important therapeutic tools for those diseases targeting tissues other than the retina.'