Descrizione del progetto
Un vaccino a RNA contro l’influenza
I vaccini a RNA appaiono come promettenti nuovi candidati per l’immunizzazione contro varie malattie, considerata la loro maggiore efficacia e i brevi tempi di produzione. Il progetto SupraRNA, finanziato dall’UE, svilupperà un approccio di vaccinazione a RNA contro i virus dell’influenza responsabili di infezioni respiratorie acute in ogni parte del mondo. Gli scienziati genereranno un sistema vettoriale per fornire un RNA messaggero mirato al gene dell’emoagglutinina (HA) del ceppo H1N1 dell’influenza A, assistito da altri peptidi per un efficace rilascio intracellulare. La convalida in vitro del potenziale di questo assemblaggio supramolecolare come vettore di consegna dell’RNA getterà le basi per i futuri sforzi verso vaccini anti-influenzali più efficaci.
Obiettivo
*The development of vaccines is key for disease prevention, and is a major focus globally in the healthcare sector. Seasonal influenza is an acute respiratory infection caused by influenza viruses which circulate in all parts of the world. Seasonally, it remains a persistent health threat and has been declared an epidemic in some states. Typical vaccines have been less effective against rapidly evolving pathogens such as influenza. A new class of vaccines based on nucleic acids, namely RNA, have recently been developed and show immense promise due to their robust nature, short manufacturing times and enhanced efficacy. Here we propose an RNA delivery system based on a supramolecular assembly approach for the vaccination of influenza A H1N1 strain. Specifically, a π-amphiphile will be used as the platform molecule for covalent RNA conjugation and delivery. A messenger RNA (mRNA) targeting the hemagglutinin (HA) gene from a model influenza virus strain will be employed as the therapeutic (H1N1/PR8-HA). The central π-amphiphile moiety will be
functionalized with the mRNA strand via a redox responsive disulfide bond, and hydrophilic oligo-oxy aryl groups connected via a hydrogen bonding unit to promote self-assembly. Steric stabilization will be afforded to the surface decorated mRNA to protect from enzymatic hydrolysis in the complex biological environments, through co-assembly with an analogue π-amphiphile which has been alternatively decorated with poly(ethylene glycol) (PEG) chains. Efficient intracellular transport of the delivery vehicle to achieve
optimum mRNA transfection will be achieved through the incorporation of a TAT-peptide on the PEG chain end. The therapeutic efficacy of the nanoassembly will be evaluated through transfection efficacy in macrophage cell lines. Overall, this proposal aims to lay the groundwork for extending the scope of RNA vaccines by exploring the potential of supramolecular assemblies as a delivery vector.
Campo scientifico
- natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acids
- natural sciencesbiological sciencesmicrobiologyvirology
- medical and health scienceshealth sciencesinfectious diseasesRNA virusesinfluenza
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines
- natural sciencesbiological sciencesgeneticsRNA
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF-EF-ST - Standard EFCoordinatore
B15 2TT Birmingham
Regno Unito