Project description
Gene therapy for adenosine deaminase deficiency
Deficiency of adenosine deaminase type 2 (DADA2) is a rare, inherited disorder characterised by abnormal inflammation of various tissues and immunodeficiency. It is caused by mutations in the ADA2 gene, rendering it an ideal candidate for gene therapy. The EU-funded DADA2GT project is exploring a gene therapy strategy for correcting ADA2 mutations in homologous haematopoietic stem cells using gene-editing technologies or gene addition by lentiviral vectors. In a clinical setting, these gene-corrected cells will be infused back to the patient. DADA2GT is a proof-of-concept study with a key goal to evaluate the efficacy of gene correction at the preclinical level using patient-derived cells.
Objective
Deficiency of adenosine deaminase type 2 (DADA2) caused by loss-of-function mutations in the ADDeficiency of adenosine deaminase type 2 (DADA2) caused by loss-of-function mutations in the ADA2 gene is a Primary immunodeficiency (PID) diseases characterized by vasculopathy, stroke, intracranial haemorrhages, systemic inflammation, immunodeficiency, and cytopenia. Without proper treatment, DADA2 patients are at high risk of severe disability or death. Targeted pharmacological therapies are not available, and generic immunosuppressive drugs are commonly used with unsatisfactory effectiveness. Haematopoietic stem cell transplantation (HSCT) has proven effective in patients with severe manifestations, but morbidity and mortality are high and hardly acceptable in less severe cases. Thus, safer and targeted therapeutic options for these patients need to be rapidly developed. Based on the observation that HSCT can be successful, it is reasonable to presume that strategies based on ADA2 correction in autologous haematopoietic stem/progenitor cells (HSPCs) may provide new targeted therapeutic approaches for DADA2. The main goal of this project is to establish gene therapy as a new therapeutic option for DADA2. We propose: i) to develop a pre-clinical approach of gene addition mediated by lentiviral vectors targeting ADA2 expression in patient HSPCs; ii) to exploit gene-editing technologies to prove their efficiency for correction of ADA2 mutations. Gene correction efficacy will be assessed as ADA2 expression and activity in vitro in HSPCs and iPSCs isolated from patients, and in mice humanized with patients’ HSPCs. Collectively, this proof-of-concept study will provide new and robust pre-clinical data for the application of lentiviral-mediated HSPC gene therapy in DADA2. This innovative research project is built upon the world-class research expertise developed by the researcher and the host institution in the areas of PIDs, autoinflammatory disorders, and genome engineering.
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.
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.
- medical and health sciences medical biotechnology genetic engineering gene therapy
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine neurology stroke
- medical and health sciences clinical medicine transplantation
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
-
H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
See all projects funded under this programme -
H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
See all projects funded under this programme
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.
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.
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.
MSCA-IF-EF-SE - Society and Enterprise panel
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.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2018
See all projects funded under this callCoordinator
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.
20132 Milano
Italy
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.