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Engineering a Sugar-targeted Nucleic Acid delivery Polymer to understand and enhance vaccination by self-amplifying RNA

Descrizione del progetto

Migliorare la somministrazione dei vaccini a base di RNA

I vaccini a base di acido nucleico si stanno affermando come alternative più scalabili ed efficaci rispetto ai vaccini convenzionali a base di proteine ricombinanti. L’RNA autoamplificante (saRNA, self-amplifying RNA) è un nuovo tipo di vaccino a RNA dotato, a quanto risulta, di una forte immunogenicità che sfrutta l’enzima virale della replicazione per autoamplificarsi. Il progetto SNAP-Vax, finanziato dall’UE, si propone di agevolare la somministrazione dei vaccini saRNA nelle cellule del sistema immunitario che presentano antigeni, introducendo un approccio più mirato per l’impiego dei vaccini. I ricercatori valuteranno diversi nanomateriali polimerici e seguiranno il destino intracellulare dei vaccini saRNA attraverso l’imaging. I risultati dovrebbero far progredire l’immunogenicità dei vaccini a base di acido nucleico.

Obiettivo

"I aim to expand the broad clinical potential of self-amplifying RNA (saRNA) vaccines by crafting nanomaterial formulations that will target intracellular delivery of saRNA and molecular adjuvants to the key cells that mediate immunity. Both the devastating SARS-CoV-2 pandemic and annual flu seasons expose a significant need for more rapid development of effective vaccines. Nucleic acids such as self-amplifying messenger RNA (saRNA) are an exciting new class of subunit vaccine cargoes that promise to address the need for more adaptable, scalable, and more efficacious vaccines in comparison to those rooted in laboriously produced recombinant proteins. Although saRNA-based vaccine production offers a powerful platform to address these major issues with vaccine development, there is a huge need for innovative methods that can deliver nucleic acids across the body's many physiological barriers and generate protective immunity. This project seeks to apply the materials expertise of the applicant and the Stevens group (Imperial College London [ICL]) to the improved delivery and function of first generation saRNA vaccines that have been pioneered in the Shattock group (ICL). We hypothesize that polymer nanomaterial design can enable delivery of saRNA vaccine components to key cells responsible for generating adaptive immune responses and that this ""targeted"" saRNA vaccine delivery will lead to enhanced protective immunity compared to current vaccines. I will apply advanced polymerization techniques to tailor the delivery of saRNA to antigen presenting cells and to master cutting-edge imaging techniques to characterize the cellular response to targeted vaccine uptake (Raman, FIB-SEM). I will then collaborate with the Shattock lab to evaluate vaccine targeting in mice in vivo and in human skin explant models ex vivo, and complete a secondment at AstraZeneca that will provide invaluable insight into translational development of nanomaterials for nucleic acid delivery."

Coordinatore

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Contribution nette de l'UE
€ 212 933,76
Indirizzo
SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
SW7 2AZ LONDON
Regno Unito

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Regione
London Inner London — West Westminster
Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 212 933,76