Description du projet
Des outils avancés de modification génétique pour une thérapie génique plus sûre
La thérapie génique offre une approche prometteuse pour traiter les maladies incurables en réduisant au silence, en activant ou en recodant des gènes spécifiques. Outre les stratégies classiques de transfert de gènes, les nouvelles technologies de modification génétique offrent la possibilité de manipuler le génome avec précision. Le projet UPGRADE, financé par l’UE, vise à remédier à certaines limites de la thérapie génique liées à la mutagenèse d’insertion, aux effets hors cible ou à une efficacité limitée. Les chercheurs mettront au point de nouvelles technologies révolutionnaires pour une modification génétique et épigénomique précise, ainsi que pour l’insertion des gènes. Après une validation rigoureuse, le projet débouchera sur des médicaments avancés et des outils polyvalents qui pourraient être utilisés pour un certain nombre de maladies.
Objectif
Gene therapy has recently shown remarkable potential to offer definitive treatments for otherwise incurable diseases. Currently, seven gene therapy products have reached the market and many more are entering clinical testing for selected indications. Moreover, emerging technologies for targeted gene editing are complementing the scope of conventional gene transfer, opening the way to precise gene correction and making possible to silence, activate or recode any sequence of interest in the genome. However, in order to realize the full potential of these strategies and broaden application of gene therapy, the field has to solve several major hurdles, including: risk of insertional mutagenesis by gene transfer vectors, limited efficiency and durability of some gene correction strategies, off target effects of editing tools, poor tissue targeting and immune response to editing components and delivery vehicles. UPGRADE will offer radical new solutions to overcome these hurdles. We will exploit and further develop disruptive new technologies for precision gene and epigenome editing and for site-specific transgene insertion, and stringently characterize their specificity and cellular responses. We will combine these improved technologies with advanced viral and non-viral vectors enabling cell/tissue targeting and immune evasion, to generate prototypes of advanced medicinal products (AMP). The safety and efficacy profile of each AMP will be stringently validated in tissues (hematopoiesis, heart and skeletal muscle, liver, retina) and disease models (muscle wasting, storage and blood disorders, hypercholesterolemia) paradigmatic for unmet medical need and potential long-term cure, if the limitations of current gene therapy strategies are overcome. These AMPs represent versatile products portable to the treatment of several other diseases because of related pathogenesis or correction strategies, thus providing the basis for tackling diseases affecting large patient groups.
Champ scientifique
- medical and health sciencesmedical biotechnologygenetic engineeringgene therapy
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugs
- medical and health sciencesbasic medicineimmunology
- medical and health sciencesclinical medicineophthalmology
- medical and health sciencesclinical medicinehematology
Mots‑clés
Programme(s)
Régime de financement
RIA - Research and Innovation actionCoordinateur
00185 Roma
Italie