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New Prime Editing and non-viral delivery strategies for Gene Therapy

Project description

An advanced gene editing approach

The past few years have witnessed advances in genome editing technologies based on the CRISPR/Cas system. Adapted from the bacterial immune defence mechanisms, the system uses RNA molecules that bind the target sequence and the Cas enzyme to cleave the DNA at the desired location. Currently, delivery of these components into cells is mediated through viral vectors that, however, present a high toxicity risk. Funded by the European Innovation Council, the EdiGenT project introduces a non-viral nanoparticle-based system with minimal side effects for the delivery of gene editing components in cells. Combined with advanced prime editor molecules, it ensures genome modification without the detrimental consequences of double strand DNA breaks.

Objective

Genome editing technologies based on CRISPR/Cas systems allow targeted genomic modification with unprecedented precision and have emerged as powerful alternatives to the conventional gene therapy approaches for various human diseases, with a series of clinical trials in progress. However, some crucial challenges remain to be addressed to enhance efficiency and safety and decrease costs of treatments.
Current viral-based delivery systems are associated with high risk of toxicity and immunogenicity and remain highly expensive. We will develop a new generation of non-viral delivery systems for gene editing tools based on the use of modified nanoparticles with human-derived protein moieties that will allow targeting the tissue and cells of interest in vivo with minimal adverse effects.
Prime editors have raised exciting possibilities for double-strand break free genome editing. However, a major limitation of current prime editors is highly variable efficiency both from one target to another and between cell types. We will design and evaluate novel prime editor tools in order to both increase activity per se and overcome cell-specific limitations.We will test our approach on the hematopoietic system to treat Sickle Cell Disease, avoiding the challenges and risks of hematopoietic stem cell manipulation associated with current gene therapy approaches, and thus providing a treatment much simpler, safer and cost-effective to implement.
Our technological breakthroughs address two key obstacles in cell and gene therapy: gene editing efficiency and systemic delivery. The novel prime editors and targeted nanoparticles that we will engineer will be combined to make unprecedented off-the-shelf, recombinant biologics for gene therapy. The versatility of the design of these novel recombinant biologics makes them suitable for the treatment of a vast majority of genetic diseases.

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HORIZON-EIC - HORIZON EIC Grants

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Call for proposal

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

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Coordinator

SORBONNE UNIVERSITE
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.

€ 861 625,00
Address
21 RUE DE L'ECOLE DE MEDECINE
75006 PARIS
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Higher or Secondary Education Establishments
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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.

€ 861 625,00

Participants (5)

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