Descripción del proyecto
Nanoestructuras y redes híbridas funcionales compensan las naturales disfuncionales
Muchas vías celulares dependen de las nanoestructuras dentro de las células. Estas vías sirven a las funciones celulares normales y protegen a las células de los patógenos a nanoescala. La comprensión de estos mecanismos de procesamiento a nanoescala relacionados con las nanoestructuras endógenas permitirá la ingeniería de nanoestructuras sintéticas o híbridas que puedan replicar los pasos del procesamiento celular. El equipo del proyecto FunctionalNanoTher, financiado por el CEI, se centrará en los mecanismos de compuerta a nanoescala que, según la hipótesis, desempeñan un papel en la defensa celular. La hipótesis es que ciertos ensamblajes moleculares actúan como «claves de acceso» que permiten la entrada intracelular a las redes biomoleculares incrustadas en las nanoestructuras. En el proyecto se intentará reproducir estas interacciones de «compuerta» para las terapias funcionales a nanoescala en el entorno tumoral.
Objetivo
We will develop new functional nanoscale medicines that engage and co-operate with cellular pathways that were designed to process and extract useful information from endogenous nanostructures, as well as protect the organism from nanoscale pathogens. We show how functional hybrid nanostructures, part-synthetic and part-cell-derived biomolecular condensate, elicit the full repertoire of cellular processing steps. In particular the enabling of highly efficient escape from endosomes and providing intracellular access to nanostructure embedded biomolecular networks. We show how cellular defences include nanoscale molecular interaction gating mechanisms that grant access on the formation of prescribed molecular assemblies that act as ‘access key codes’. The assembled molecular interactions at these gates may be captured and analysed using time-resolved spatially localized chemical reactions within the cell, and the enabling assemblies analysed in molecular detail. The cell-derived condensate portion of the hybrid particles may be re-engineered to incorporate foreign proteins and RNAs, while retaining overall function, and the new biomolecules can then be delivered to intracellular locations with their function intact. These advances make it possible to understand the connection between nanostructure architecture and function, and thereby open the pathway to recapitulate the functional nanostructures using purely preparative methods. To apply these systems we first propose to use functional nanostructures to deliver specifically optimised mRNA for Covid-19 spike protein into the cell, optimising mRNA metabolism to benefit from endogenous intracellular access. We then propose to engineer and deliver cooperative networks of multiple mRNA, with the prospect of being able to develop functional nanoscale therapies that can counter more extended dysfunctional networks such as those found in the tumour microenvironment.
Ámbito científico
Palabras clave
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-ERC - HORIZON ERC GrantsInstitución de acogida
4 Dublin
Irlanda