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

Description du projet

Améliorer l’administration des vaccins à base d’ARN

Face aux vaccins traditionnels qui utilisent des protéines recombinantes, les vaccins à base d’acide nucléique sont des solutions qui présentent une meilleure évolutivité et efficacité. L’ARN auto-amplifiant (ARNa) est un nouveau type de vaccin à ARN, à qui l’on attribue une forte immunogénicité, qui exploite l’enzyme de réplicase virale pour s’amplifier. Le projet SNAP-Vax, financé par l’UE, entend faciliter l’administration de vaccins à ARNa dans les cellules présentatrices d’antigènes du système immunitaire, en tant qu’approche plus ciblée de l’utilisation des vaccins. Les chercheurs évalueront différents nanomatériaux polymères et suivront le devenir intracellulaire des vaccins à ARNa grâce à l’imagerie. Les résultats devraient faire avancer l’immunogénicité des vaccins à base d’acide nucléique.

Objectif

"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."

Coordinateur

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Contribution nette de l'UE
€ 212 933,76
Adresse
SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
SW7 2AZ LONDON
Royaume-Uni

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Région
London Inner London — West Westminster
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
€ 212 933,76