Description du projet
La modification génétique est sur la bonne voie grâce à l’algèbre booléenne
Nous utilisons des opérateurs booléens partout. Ces simples «tests» de conditions (si A «ET» B est vrai, si A «OU» B est vrai, etc.) sont utilisés pour tout: dans la programmation de logiciels, les moteurs de recherche des bases de données ou même les décisions logiques que nous prenons au quotidien sans nous en rendre compte. Désormais, I-GENE applique la logique booléenne et des nanotransducteurs à la modification génétique pour en renforcer considérablement la sécurité. Las nanotransducteurs sont des particules minuscules pouvant transformer l’énergie en un signal. En utilisant des fonctions ET à plusieurs entrées qui requièrent l’activation d’un nanotransducteur et la reconnaissance de plusieurs loci de gènes spécifiques, I-GENE prévoit de verrouiller la cible adéquate pour atteindre une modification génétique sûre et précise et étendre son utilisation thérapeutique.
Objectif
CRISPR/Cas9 and enzyme-based editors hold promise for genome surgery by erasing harmful mutations and re-writing in helpful ones, but face critical barriers related to safety. Here, we propose a new concept of genome engineering based on nanotransducers (NT), which aims to make safe previously impracticable applications of genome editing and transcriptional regulation by Cas9. The methodology is based on laser-activation of a NT, which triggers a thermo-switchable double strand DNA break or cleavage. The proposed technology implements a concept of multi-input AND gates, where the output (gene editing) is true if multiple inputs are true (e.g. NT activation and recognition of 2 different loci). Indeed, the dream of unique recognition of the desired genomic target from any potential off-targets in the 3 billion base pairs of human genome would be possible. The superiority of I-GENE technology over current methodologies lies also in the multi-function integration, i.e. integration of the time function (editing only when the laser is on), the spatial function (editing only where the laser is focused) and the fidelity function (editing only if on-target) (when-where-if functions integration). Overall, this enables temporal control of single cell editing and provides an absolute safety level for developing effective genome editing for biotechnology and therapeutic applications. In the present project, proof on concept studies for technology optimization will be performed on non-mammalian zebrafish embryos. Subsequently, the therapeutic potential will be validated in a murine model of melanoma. I-GENE technology would push the boundaries of efficient and reliable ways to make precise, targeted changes to the genome of living cells that is the long-standing and main goal of gene therapy and biomedical researchers.
Champ scientifique
- medical and health sciencesmedical biotechnologygenetic engineeringgene therapy
- medical and health sciencesclinical medicineoncologyskin cancermelanoma
- medical and health sciencesclinical medicineembryology
- natural sciencesbiological sciencesgeneticsgenomes
- natural sciencesphysical sciencesopticslaser physics
Mots‑clés
Programme(s)
Régime de financement
RIA - Research and Innovation actionCoordinateur
56126 Pisa
Italie