Skip to main content
Go to the home page of the European Commission (opens in new window)
English English
CORDIS - EU research results
CORDIS

Next-generation AAV vectors for liver-directed gene therapy

Project description

Novel adeno-associated vectors for liver gene transfer

Recombinant adeno-associated vectors (AAV) achieved remarkable success in recent clinical trials for liver gene transfer. However, several hurdles prevent expansion of AAV-mediated therapy to all patients, including transient AAV-mediated expression in proliferating hepatocytes due to episomal AAV genome dilution, hepatotoxicity and immune response against AAVs, and pre-existing immunity to AAV capsids. The EU-funded AAVolution project proposes to find novel small Cas nucleases for in vivo AAV-mediated genome editing with self-replicating episomal AAVs. The aim is to avoid transgene dilution, create synthetic AAVs with reduced toxicity and develop technologies to overcome pre-existing immunity to AAVs. The novel tool set will enable broad expansion of AAV-mediated gene therapy for indications beyond rare diseases.

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.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.

You need to log in or register to use this function

Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

HORIZON-EIC - HORIZON EIC Grants

See all projects funded under this funding scheme

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) HORIZON-EIC-2021-PATHFINDERCHALLENGES-01

See all projects funded under this call

Coordinator

FONDAZIONE TELETHON ETS
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 137 600,00
Address
VIA VARESE 16/B
00185 ROMA
Italy

See on map

Region
Centro (IT) Lazio Roma
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 192 600,00

Participants (9)

My booklet 0 0