Descripción del proyecto
Avances en la manipulación genética «ex vivo» de células madre hematopoyéticas
Las células madre hematopoyéticas (CMH) son células multipotentes capaces de diferenciarse en cualquier linaje hematopoyético. Sin embargo, los métodos de la terapia génica dependen de una población celular enriquecida en CMH, ya que estas células no pueden aislarse de forma prospectiva. El equipo del proyecto X-PAND, financiado por el Consejo Europeo de Innovación, propone desarrollar una plataforma «ex vivo» para el cultivo, la expansión y la modificación genética de CMH. El método X-PAND será de alto rendimiento y contará con un tiempo de respuesta rápido, lo cual permitirá optimizar los protocolos de terapia génica sin necesidad de laboriosos experimentos de trasplante «in vivo» en ratones. Los investigadores se centrarán en los síndromes hereditarios de insuficiencia de la médula ósea y el cáncer, pero se prevé ampliar el método a otras enfermedades y asegurar el resultado de las terapias génicas.
Objetivo
Hematopoietic stem cells (HSC) are an elusive cell type, whose presence can only be inferred retrospectively, from the outcome of time-consuming transplantation experiments. Since current state-of-the-art does not allow prospective HSC identification, today’s cell and gene therapy technology has been mostly optimized on surrogate progenitor cells, which differ biologically from HSC. The technological breakthrough of this proposal is to capture HSC in the ex vivo culture, achieved by a combination of innovative expansion conditions, iterative cell sorting and multiomics single cell profiling. Rapid, quantitative and qualitative in vitro HSC assessment predictive of in vivo function may become a sustainable alternative to mouse xenotransplantation experiments. Applied to a state-of-the-art toolbox of genetic engineering technologies including clinically-proven lentiviral vectors as well as established and emerging targeted genome editing approaches, our in vitro HSC readout sets new standards in terms of throughput and turnaround time, allowing to efficiently test a multitude of HSC engineering conditions and tailor the most suitable technological approach to a specific disease or therapeutic application. This new precision-based approach to ex vivo HSC gene therapy will be applied to inherited bone marrow failure syndromes and cancer as paradigmatic examples where gene therapy may be used to correct a cell-intrinsic genetic defect or turn hematopoietic progeny into therapeutic vehicles provided with novel functions. Bringing together experts in cutting-edge gene editing technologies, ex vivo HSC manipulation, assessment of HSC responses to genetic engineering and bioinformatics analysis & integration of multi-dimensional single cell data will maximize the chances of delivering safer and more effective next-generation HSC-based gene therapy products, extending the reach of gene therapy to new disease contexts and making the outcome after gene therapy more predictable.
Ámbito científico
- medical and health sciencesmedical biotechnologygenetic engineeringgene therapy
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- medical and health sciencesclinical medicineoncology
- medical and health sciencesclinical medicinetransplantation
- natural sciencesbiological sciencesgeneticsgenomes
Palabras clave
Programa(s)
- HORIZON.3.1 - The European Innovation Council (EIC) Main Programme
Tema(s)
Convocatoria de propuestas
HORIZON-EIC-2021-PATHFINDERCHALLENGES-01
Consulte otros proyectos de esta convocatoriaRégimen de financiación
HORIZON-EIC - HORIZON EIC GrantsCoordinador
20132 Milano
Italia