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Next-generation AAV vectors for liver-directed gene therapy

Objective

Liver-directed gene therapy has undergone significant development in the last two decades. Recombinant adeno-associated vectors (AAV) are the vectors of choice for liver gene transfer and have recently achieved remarkable successes in clinical trials. However, there are still large groups of patients who have limited access to therapy. The major hurdles toward expanding the indication of AAV-mediated liver gene therapy are: i) transient AAV-mediated expression in proliferating hepatocytes, i.e. newborn or regenerating livers, due to dilution of episomal AAV genome in proliferating cells; ii) dose-dependent hepatotoxicity and immune response against AAVs; and iii) pre-existing immunity to AAV capsids, which currently preclude its systemic delivery in about 50% of individuals. AAVolution gathers renowned European experts in the field of AAV vectorology, gene therapy, genome editing and immunology, with the ambitious goal to develop and implement innovative therapeutic tools to effectively address these challenges. To this aim AAVolution proposes: i) to seek novel small Cas nucleases for in vivo AAV-mediated genome editing ii)to develop self-replicating episomal AAVs to avoid transgene dilution in proliferating livers; iii) to generate synthetic AAVs characterized by enhanced potency and reduced toxicity, by screening of novel AAV capsid libraries; iv) and to develop improved technologies to overcome pre-existing immunity to AAVs by transiently reducing the levels of circulating anti-AAV neutralizing antibodies.
AAVolution will significantly expand the toolkit for AAV-mediated liver gene therapy, developing novel and improved molecular instruments to address the most relevant hurdles toward safer and more effective therapies, and provide access to treatment to patients that are currently excluded from clinical trials. Moreover, these novel tools will constitute an innovative platform with a potential for broad expansion of disease indications beyond the rare diseases.

Coordinator

FONDAZIONE TELETHON ETS
Net EU contribution
€ 1 087 600,00
Address
Via Varese 16/b
00185 Roma
Italy

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Region
Centro (IT) Lazio Roma
Activity type
Research Organisations
Non-EU contribution
€ 0,00

Participants (8)

Third-party

Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure.

INNOVAVECTOR SRL
Italy
Net EU contribution
€ 40 000,00
Address
Via Campi Flegrei 34
80078 Pozzuoli

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SME

The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.

Yes
Region
Sud Campania Napoli
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 0,00
Third-party

Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure.

NEXT GENERATION DIAGNOSTIC SRL
Italy
Net EU contribution
€ 15 000,00
Address
Via Campi Flegrei 34
80078 Pozzuoli

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SME

The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.

Yes
Region
Sud Campania Napoli
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 0,00
ASSOCIATION GENETHON
France
Net EU contribution
€ 591 000,00
Address
Rue De L Internationale 1 Bis
91002 Evry

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Region
Ile-de-France Ile-de-France Essonne
Activity type
Research Organisations
Non-EU contribution
€ 0,00
UNIVERSITA DEGLI STUDI DI TRENTO
Italy
Net EU contribution
€ 551 600,00
Address
Via Calepina 14
38122 Trento

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Region
Nord-Est Provincia Autonoma di Trento Trento
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
FUNDACION PARA LA INVESTIGACION MEDICA APLICADA FIMA
Spain
Net EU contribution
€ 551 600,00
Address
Avenida De Pio Xii 55
31008 Pamplona

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Region
Noreste Comunidad Foral de Navarra Navarra
Activity type
Research Organisations
Non-EU contribution
€ 0,00
MEDIZINISCHE HOCHSCHULE HANNOVER
Germany
Net EU contribution
€ 512 200,00
Address
Carl-neuberg-strasse 1
30625 Hannover

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Region
Niedersachsen Hannover Region Hannover
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
CINFERENCE UG
Germany
Net EU contribution
€ 257 000,00
Address
Rheinsberger Strasse 76/77 C/o Fact
10115 Berlin

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SME

The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.

Yes
Region
Berlin Berlin Berlin
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 0,00
UNIVERSITA DEGLI STUDI DI NAPOLI FEDERICO II
Italy
Net EU contribution
€ 394 000,00
Address
Corso Umberto I, 40
80138 Napoli

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Region
Sud Campania Napoli
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00