Kits for advanced polymer-lipid nanocarriers for targeted delivery of RNAs to cardiac and skeletal muscle cells

Informations projet

POLIRNA

N° de convention de subvention: 101113522

DOI

10.3030/101113522

Projet clôturé

Date de signature de la CE 20 Mars 2023

Date de début 1 Octobre 2023

Date de fin 31 Mars 2025

Financé au titre de

• European Research Council (ERC)

Coût total

Aucune donnée

Contribution de l’UE

€ 150 000,00

Coordonné par

POLITECNICO DI TORINO
Italy

Periodic Reporting for period 1 - POLIRNA (Kits for advanced polymer-lipid nanocarriers for targeted delivery of RNAs to cardiac and skeletal muscle cells)

Période du rapport: 2023-10-01 au 2025-03-31

Résumé du contexte et des objectifs généraux du projet

RNAs are new frontiers drugs with remarkable therapeutic potential for the development of new advanced therapies. However, the potentialities of RNA molecules cannot be fully exploited using traditional lipid nanoparticles which suffer from low stability in physiological media, uncontrolled release, possibility to provoke an immune response in vivo and main accumulation into the liver. POLIRNA project was aimed at addressing the need for safe, effective, user-friendly, versatile nanoparticles for the delivery of RNA molecules to specific cell types for research use in the testing of new potential RNA therapies. The aim was achieved by the design and validation of novel hybrid nanoparticles, consisting of: a lipidic core for efficient RNA loading, a polymeric shell to improve stability and controlled drug delivery, and surface grafted molecules for the specific release of loaded RNA molecules to target cells, with a focus on cardiac and skeletal muscle cells.
POLIRNA nanoparticles were intended for use in research as novel cell-specific “transfection vectors” for the delivery of RNA molecules. The user-friendly preparation and superior properties of POLIRNA nanoparticles as RNA delivery systems make them promising for use in the preclinical validation of new therapeutic RNAs. The establishment of partnerships with companies and/or research groups proprietary of new RNA molecules will also pay the way to the development of new advanced therapy medicinal products for cardiac regenerative medicine and the treatment of muscle-related pathologies, such as neuromuscular diseases.
In POLIRNA project hybrid nanoparticles were extensively characterized both in vitro and by preliminary in vivo biodistribution tests in mouse models. The technology was also patented.
A startup company called PoliRNA Srl was founded in Turin in Feb. 2024 by three POLIRNA team members to exploit the hybrid nanoparticle technology and translate it into the market. PoliRNA Srl was recognized as spinoff company of Politecnico di Torino in Jul. 2024. The company participated in multiple entrepreneurship competitions receiving coaching from expert mentors for the development of an effective business plan, and winning different relevant prizes.

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

During the project, the main technical and scientific achievements were:
1) The development of transfection kits for the user-friendly preparation of hybrid nanoparticles by users involved in research activities on RNA delivery to cardiac and skeletal muscle cells. Extensive efforts were dedicated to the optimization of the surface functionalization of POLIRNA hybrid nanoparticles with molecules enabling the targeted release of RNA molecules to specific cardiac and skeletal muscle cells.
2) The physicochemical characterization of POLIRNA hybrid nanoparticles, including the definition of sterilization and storage methods after their preparation.
3) The preclinical validation of the safety and efficacy of POLIRNA hybrid nanoparticles using relevant cell lines and novel in vitro tissue models.
4) A preliminary in vivo characterization of the biodistribution of POLIRNA hybrid nanoparticles in mouse models.
5) The foundation of a startup company for the exploitation of the technology.
At the end of the project, POLIRNA nanoparticles reached a technology readiness level of 4.

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)

POLIRNA hybrid nanoparticles are expected to expand the application of RNA therapies beyond use as Covid-19 vaccines and for the treatment of liver-related diseases which are the two main applications of clinically approved RNA therapies to date. However further research and demonstration is needed for the optimization and preclinical validation of surface functionalized hybrid nanoparticles in order to ensure high cell selectivity and enhanced safety. The project allowed to consolidate and establish collaborations with research groups committed to the development of new therapeutic RNAs, Pharma and Biotech companies. PoliRNA Srl is currently in search for founding to further validate the technology. The team is also exploring the potentiality of hybrid nanoparticles for other emerging targeted RNA therapies addressed to cancer and immune cells.
POLIRNA is expected to contribute to the development of new RNA therapies for treating cardiac and skeletal muscle-related diseases, widening the applications of RNA therapies.