RNA-protein Nanostructures for Synthetic Biology

Informations projet

RNA ORIGAMI

N° de convention de subvention: 683305

DOI

10.3030/683305

Projet clôturé

Date de signature de la CE 29 Mars 2016

Date de début 1 Avril 2016

Date de fin 31 Mars 2021

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 1 999 935,00

Contribution de l’UE

€ 1 999 935,00

Coordonné par

AARHUS UNIVERSITET
Denmark

Periodic Reporting for period 4 - RNA ORIGAMI (RNA-protein Nanostructures for Synthetic Biology)

Période du rapport: 2020-10-01 au 2021-03-31

Résumé du contexte et des objectifs généraux du projet

The RNA ORIGAMI project aimed at rationally designing RNA nanostructures that can be genetically expressed and function as scaffolds for controlling e.g. protein function in cells. This technology can potentially be used for a wide range of applications in synthetic biology such as production of cheaper drugs, sustainable fuel production, efficient diagnosis, and RNA medicine. The main objectives of the project were to develop design software, to characterize designed RNA scaffolds, to develop RNA sensor devices, and to demonstrate proof-of-concept applications in synthetic biology. The project succeeded in developing software tools to improve size, yield and functionalization of RNA nanostructures, demonstrated novel RNA sensors, and applied RNA nanostructures in metabolic engineering.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

The RNA ORIGAMI project initially developed software for the rapid design of RNA origami structures and used biophysical characterization techniques to verify the folding of the designed structures. The software has been made publicly available in a code repository and as a webserver and has been used for obtain several research results: (1) RNA sensors were developed based on Förster Resonance Energy Transfer (FRET) between fluorescent aptamers, (2) RNA therapeutic particles were developed to control blood coagulation, (3) RNA scaffolds were used to stabilize functional motifs in E. coli cells, (4) RNA scaffolds were used to control enzymatic reactions in E. coli and yeast. These core results are being exploited for RNA medicine and metabolic engineering and have been or are in the process of being published in the scientific literature.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The RNA ORIGAMI project has improved our ability to construct genetically expressible RNA nanostructures. We have improving folding yield, reached construct sizes of 2000 bases in length, and demonstrated precise scaffolding of proteins and small molecules. The development of an aptamer-based FRET system has provided a new way to develop genetically expressible sensors systems and to measure conformational changes in cells. RNA origami has been demonstrated as a powerful tool in synthetic biology by stabilizing functional motifs in cells, by regulating protein expression, and by controlling enzymatic pathways.

RNA origami folding