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

Descripción del proyecto

Mejora de la administración de las vacunas de ARN

Las vacunas de ácidos nucleicos están surgiendo como una alternativa más escalable y eficaz a las vacunas convencionales con proteínas recombinantes. Las vacunas de ARN autorreplicativo (saRNA, por sus siglas en inglés), son un nuevo tipo de vacuna de ARN con una gran inmunogenicidad que, según se ha descrito, aprovecha la enzima replicasa vírica para amplificarse. El objetivo del proyecto SNAP-Vax, financiado con fondos europeos, es facilitar la administración de vacunas de saRNA en células presentadoras de antígenos del sistema inmunitario como un método más específico para la inmunización. Sus investigadores evaluarán diferentes nanomateriales poliméricos y realizarán un seguimiento del destino intracelular de las vacunas de saRNA mediante imagenología. Se espera que los resultados mejoren la inmunogenicidad de las vacunas de ácidos nucleicos.

Objetivo

"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."

Coordinador

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Aportación neta de la UEn
€ 212 933,76
Dirección
SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
SW7 2AZ LONDON
Reino Unido

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Región
London Inner London — West Westminster
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
€ 212 933,76