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

Descripción del proyecto

Un método avanzado de edición genómica

En los últimos años, se han producido avances en las tecnologías de edición genómica basadas en el sistema CRISPR/Cas. Este sistema, adaptado a partir de los mecanismos de defensa de la respuesta inmunitaria bacteriana, utiliza moléculas de ARN que unen la secuencia diana con la enzima Cas para escindir el ADN en el lugar deseado. En la actualidad, la introducción de estos componentes en las células se lleva a cabo a través de vectores víricos, aunque estos presentan un elevado riesgo de toxicidad. El equipo del proyecto EdiGenT, financiado por el Consejo Europeo de Innovación, presenta un sistema basado en nanopartículas no víricas con efectos secundarios mínimos para la introducción de componentes de edición genómica en las células. El sistema, combinado con las principales moléculas editoras avanzadas, garantiza la modificación del genoma sin las consecuencias perjudiciales de las roturas de la doble cadena de ADN.

Objetivo

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.

Régimen de financiación

HORIZON-EIC - HORIZON EIC Grants

Coordinador

SORBONNE UNIVERSITE
Aportación neta de la UEn
€ 861 625,00
Dirección
21 RUE DE L'ECOLE DE MEDECINE
75006 Paris
Francia

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Región
Ile-de-France Ile-de-France Paris
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
€ 861 625,00

Participantes (5)