Descrizione del progetto
L’editing genetico raggiunge l’obiettivo grazie all’algebra booleana
Utilizziamo gli operatori booleani praticamente ovunque. Questi semplici «test» di condizioni, se A «AND» B sono veri, se A «OR» B è vero, e così via, vengono utilizzati per tutto, dalla programmazione di software ai motori di ricerca dei database, fino alle decisioni logiche che prendiamo quotidianamente senza nemmeno rendercene conto. Ora, I-GENE sta applicando la logica booleana e i nanotrasduttori all’editing genetico per migliorare significativamente la sicurezza. I nanotrasduttori sono minuscole particelle che riescono a convertire l’energia in un segnale. Utilizzando porte AND multi-ingresso che richiedono l’attivazione di nanotrasduttori AND il riconoscimento di loci genetici specifici multipli, I-GENE prevede di fissare l’obiettivo corretto per un editing genetico preciso e sicuro e un uso terapeutico esteso.
Obiettivo
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.
Campo scientifico
- 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
Parole chiave
Programma(i)
Invito a presentare proposte
Vedi altri progetti per questo bandoBando secondario
H2020-FETOPEN-2018-2019-2020-01
Meccanismo di finanziamento
RIA - Research and Innovation actionCoordinatore
56126 Pisa
Italia