Descrizione del progetto
Progressi nella manipolazione genetica ex vivo delle cellule staminali ematopoietiche
Le cellule staminali ematopoietiche (CSE) sono cellule multipotenti che possono differenziarsi in qualsiasi linea ematopoietica, ma i metodi che sfruttano la terapia genica si basano su una popolazione cellulare arricchita di CSE, poiché queste non possono essere isolate in maniera prospettiva. Il progetto X-PAND, finanziato dal Consiglio europeo per l’innovazione, si propone di sviluppare una piattaforma ex vivo per la coltura, l’espansione e l’ingegneria genetica delle CSE. Il metodo X-PAND avrò un alto rendimento e tempi di completamento rapidi, e consentirà di ottimizzare i protocolli di terapia genica senza dover ricorrere a laboriosi esperimenti di trapianto in vivo nei topi. I ricercatori si concentreranno sulle sindromi da insufficienza del midollo e sul cancro ereditari, ma il piano prevede di estendere il metodo ad altre patologie e di garantire i risultati delle terapie geniche.
Obiettivo
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.
Campo scientifico
- 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
Parole chiave
Programma(i)
- HORIZON.3.1 - The European Innovation Council (EIC) Main Programme
Argomento(i)
Invito a presentare proposte
HORIZON-EIC-2021-PATHFINDERCHALLENGES-01
Vedi altri progetti per questo bandoMeccanismo di finanziamento
HORIZON-EIC - HORIZON EIC GrantsCoordinatore
20132 Milano
Italia