TARGETINGGENETHERAPY

Towards Safe and Effective Hematopoietic Stem Cell Gene Therapy: Targeting Integration to Genomic Safe Harbors and Exploiting Endogenous microRNA to Regulate Transgene Expression

Coordinatore	UNIVERSITA VITA-SALUTE SAN RAFFAELE    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Italy [IT]
Totale costo	2˙500˙000 €
EC contributo	2˙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-2009-AdG
Funding Scheme	ERC-AG
Anno di inizio	2010
Periodo (anno-mese-giorno)	2010-05-01   -   2016-01-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	Ospedale San Raffaele  Organization address address: Via Olgettina 60 city: Milano postcode: 20132 contact info Titolo: Dr. Nome: Maria Rosa Cognome: Pedrazzi Email: send email Telefono: +39 02 2643 4845 Fax: +39 02 2643 4717	IT (Milano)	beneficiary	1˙096˙197.87
2	FONDAZIONE CENTRO SAN RAFFAELE DEL MONTE TABOR  Organization address address: Via Olgettina 60 city: MILANO postcode: 20132 contact info Titolo: Mr. Nome: Mario Cognome: Valsecchi Email: send email Telefono: +39 02 26432729 Fax: +39 02 26432752	IT (MILANO)	beneficiary	493˙002.13
3	UNIVERSITA VITA-SALUTE SAN RAFFAELE  Organization address address: Via Olgettina 58 city: MILANO postcode: 20132 contact info Titolo: Dr. Nome: Maria Rosa Cognome: Pedrazzi Email: send email Telefono: +39 02 26434845 Fax: +39 02 2643 4717	IT (MILANO)	hostInstitution	910˙800.00
4	UNIVERSITA VITA-SALUTE SAN RAFFAELE  Organization address address: Via Olgettina 58 city: MILANO postcode: 20132 contact info Titolo: Prof. Nome: Luigi Cognome: Naldini Email: send email Telefono: +39 02 2643 4681 Fax: +39 02 2643 4621	IT (MILANO)	hostInstitution	910˙800.00

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 Obiettivo del progetto (Objective)

'Hematopoietic stem cell gene therapy has a tremendous potential to treat human disease. Yet, in conjunction with the first successful results in the clinic, severe adverse events linked to the gene transfer protocol were reported. Recently, we provided proof-of-principle of two new powerful strategies to improve the efficacy and safety of gene transfer: 1) regulating transgene expression by exploiting cellular microRNAs; 2) targeting integration at predetermined sites of the genome by forcing homologous recombination with designer Zinc finger nucleases. Here we will investigate the microRNA network regulating hematopoiesis and exploit the new knowledge to develop vectors with stringently controlled expression throughout the hematopoietic lineages. We will develop Zinc finger nuclease-based vectors that insert the transgene with high efficiency and specificity either downstream to its own endogenous promoter or into a safe genomic harbor that allows for robust expression without interference on the neighboring genes. By combining these strategies we will provide radically improved gene transfer platforms. Furthermore, we will exploit these technologies for the generation and genetic correction of induced pluripotent stem cells, providing a potentially unlimited source of patient-derived vector free gene corrected multipotent stem cells for future applications of regenerative medicine. The new gene therapy strategies will be tested in pre-clinical models of leukodystrophies and immunodeficiencies, for which we have extensive experience, and should enter a clinical trial for at least one such disease by the end of the proposed funding period. If successfully validated, the new strategies may eventually broaden the scope of gene therapy in medicine.'