Project description
Evaluation of genome-editing therapies for sickle cell disease
Sickle cell disease (SCD) is a result of a single amino acid substitution in the beta-globin chain of adult haemoglobin. The severity of SCD is alleviated by the co-inheritance of mutations driving the expression of foetal gamma-globin in adults. Transplantation of autologous, genetically modified haematopoietic stem/progenitor cells (HSPC) represents a therapeutic option for SCD. The EU-funded EDITSCD project aims to understand the molecular and cellular mechanisms underlying SCD HSPC dysfunctions and evaluate the impact of genome editing approaches on SCD HSPC. The study objective is to improve the SCD gene therapy strategy and evaluate the best tools and protocols for genome editing HSPC therapies.
Objective
Sickle cell disease (SCD) is one of the most prevalent monogenic diseases in Europe. A single amino acid substitution in the beta-globin chain of the adult hemoglobin (Hb) drives red blood cell sickling and multi-organ damage. The clinical severity of SCD is alleviated by the co-inheritance of mutations causing expression of fetal gamma-globin in adult life ? a condition termed hereditary persistence of fetal hemoglobin (HPFH). Transplantation of autologous, genetically modified hematopoietic stem/progenitor cells (HSPCs) is an attractive therapeutic option for SCD patients. To this end, genome editing approaches based on the use of site-specific nucleases or, more recently, base editors have been explored by many groups, including teams in our consortium. These approaches either correct the single point mutation causing SCD or reactivate fetal gamma-globin expression by mimicking HPFH mutations. On the other hand, (pre)clinical data from SCD patients or SCD mouse models, as well as preliminary data from our labs suggest that SCD HSPCs are characterized by a high mutational burden, oxidative stress and expression of inflammatory genes. This can alter HSPC properties as well as their interactions within the bone marrow niche. In the context of gene therapy, it is essential to understand the mechanisms underlying SCD HSPC dysfunction and assess the impact of genome editing approaches on SCD HSPCs. In this proposal, we have assembled a multidisciplinary team to: (i) understand the molecular and cellular mechanisms underlying SCD HSPC autonomous and non-cell-autonomous dysfunctions and (ii) evaluate the impact of established and novel genome editing approaches on SCD HSPC properties and genome integrity. This study will lay the foundation of an improved gene therapy strategy to treat SCD and provide best practice tools and protocols for genome editing-based therapies in HSPCs.
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.
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine transplantation
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.2.1 - Health
MAIN PROGRAMME
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HORIZON.2.1.5 - Tools, Technologies and Digital Solutions for Health and Care, including personalised medicine
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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.
HORIZON-RIA - HORIZON Research and Innovation Actions
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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) HORIZON-HLTH-2021-TOOL-06
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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.
75015 Paris
France
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.