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IMPROVING-GT

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Cerrado

Innovative strategies to increase engraftment of engineered hematopoietic stem c...

Innovative strategies to increase engraftment of engineered hematopoietic stem cells and bypass genotoxic conditioning toward the next generation gene therapy Hematopoietic stem/progenitor cell gene therapy (HSPC-GT) refers to the transfer of nucleic acids into HSPCs, to either add a new copy of a healthy gene or to correct a mutated gene. HSPC-GT is successfully used in clinic to treat... ver más

31/12/2023

OSR

183K€

Presupuesto del proyecto: 183K€

Líder del proyecto

OSPEDALE SAN RAFFAELE SRL No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2023-12-31

MSCA-IF-2020: Individual Fellowships

I+D

Cerrada hace 4 años

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Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

1 Participantes

OSR

183.47K€ | Lider

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Duración del proyecto: 32 meses Fecha Inicio: 2021-04-22
Fecha Fin: 2023-12-31

Líder del proyecto

OSPEDALE SAN RAFFAELE SRL No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 183K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Hematopoietic stem/progenitor cell gene therapy (HSPC-GT) refers to the transfer of nucleic acids into HSPCs, to either add a new copy of a healthy gene or to correct a mutated gene. HSPC-GT is successfully used in clinic to treat patients with hematopoietic malignancies and several inherited diseases of the hematopoietic system. Yet, its current use is accompanied by acute conditioning-related toxicities, which impose a burden on patients and limit its application to the most severe conditions. HSPC-GT requires the following steps: HSPCs are mobilized and harvested from the patient, genetically corrected ex-vivo by gene transfer or gene editing and infused back to the patient, after administration of partial or fully myeloablative conditioning to make space in the bone marrow for the modified cells. Administered HSPCs home to the bone marrow, where they engraft and reconstitute a healthy immune system, theoretically throughout life. However, two major shortcomings undermine the full therapeutic potential of HSPC-GT: (i) a decrease in short- and/or long-term engraftment potential due to the ex vivo manipulation of HSPCs and (ii) a toxicity in the hematopoietic and non-hematopoietic organs related to the conditioning regimens, which are based on cytotoxic drugs. The project IMPROVING-GT proposes to develop innovative schemes to increase engraftment and dodge genotoxic conditioning, which are some of the most coveted but still unaccomplished goals of HSPC-GT. The candidate aims to (1) increase the fitness of genetically modified HSPCs by uncovering new players of engraftment and (2) bypass the toxic conditioning requirement by exploiting enhanced mobilization reagents. IMPROVING-GT will pave the way towards non or milder genotoxic regimens, which should greatly minimize undesirable toxicity of current treatments and ameliorate patients’ outcome. Moreover, it may help broadening applications of HSPC-GT to more diseases, including patients with lower disease burden.

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