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Engineering a Novel Modular Adenoviral mRNA Delivery Platform Based on Tag/Catcher Bioconjugation

mRNA vaccines have attracted widespread research attention with clear advantages in terms of molecular flexibility, rapid development, and potential for personalization. However, current mRNA vaccine platforms have not been optimized for induction of CD4/CD8 T cell responses. In addition, the mucosa...

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Autores principales: Geng, Kexin, Rice-Boucher, Paul J., Kashentseva, Elena A., Dmitriev, Igor P., Lu, Zhi Hong, Goedegebuure, S. Peter, Gillanders, William E., Curiel, David T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674448/
https://www.ncbi.nlm.nih.gov/pubmed/38005953
http://dx.doi.org/10.3390/v15112277
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author Geng, Kexin
Rice-Boucher, Paul J.
Kashentseva, Elena A.
Dmitriev, Igor P.
Lu, Zhi Hong
Goedegebuure, S. Peter
Gillanders, William E.
Curiel, David T.
author_facet Geng, Kexin
Rice-Boucher, Paul J.
Kashentseva, Elena A.
Dmitriev, Igor P.
Lu, Zhi Hong
Goedegebuure, S. Peter
Gillanders, William E.
Curiel, David T.
author_sort Geng, Kexin
collection PubMed
description mRNA vaccines have attracted widespread research attention with clear advantages in terms of molecular flexibility, rapid development, and potential for personalization. However, current mRNA vaccine platforms have not been optimized for induction of CD4/CD8 T cell responses. In addition, the mucosal administration of mRNA based on lipid nanoparticle technology faces challenges in clinical translation. In contrast, adenovirus-based vaccines induce strong T cell responses and have been approved for intranasal delivery. To leverage the inherent strengths of both the mRNA and adenovirus platforms, we developed a novel modular adenoviral mRNA delivery platform based on Tag/Catcher bioconjugation. Specifically, we engineered adenoviral vectors integrating Tag/Catcher proteins at specific locales on the Ad capsid proteins, allowing us to anchor mRNA to the surface of engineered Ad viruses. In proof-of-concept studies, the Ad-mRNA platform successfully mediated mRNA delivery and could be optimized via the highly flexible modular design of both the Ad-mRNA and protein bioconjugation systems.
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spelling pubmed-106744482023-11-20 Engineering a Novel Modular Adenoviral mRNA Delivery Platform Based on Tag/Catcher Bioconjugation Geng, Kexin Rice-Boucher, Paul J. Kashentseva, Elena A. Dmitriev, Igor P. Lu, Zhi Hong Goedegebuure, S. Peter Gillanders, William E. Curiel, David T. Viruses Article mRNA vaccines have attracted widespread research attention with clear advantages in terms of molecular flexibility, rapid development, and potential for personalization. However, current mRNA vaccine platforms have not been optimized for induction of CD4/CD8 T cell responses. In addition, the mucosal administration of mRNA based on lipid nanoparticle technology faces challenges in clinical translation. In contrast, adenovirus-based vaccines induce strong T cell responses and have been approved for intranasal delivery. To leverage the inherent strengths of both the mRNA and adenovirus platforms, we developed a novel modular adenoviral mRNA delivery platform based on Tag/Catcher bioconjugation. Specifically, we engineered adenoviral vectors integrating Tag/Catcher proteins at specific locales on the Ad capsid proteins, allowing us to anchor mRNA to the surface of engineered Ad viruses. In proof-of-concept studies, the Ad-mRNA platform successfully mediated mRNA delivery and could be optimized via the highly flexible modular design of both the Ad-mRNA and protein bioconjugation systems. MDPI 2023-11-20 /pmc/articles/PMC10674448/ /pubmed/38005953 http://dx.doi.org/10.3390/v15112277 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Geng, Kexin
Rice-Boucher, Paul J.
Kashentseva, Elena A.
Dmitriev, Igor P.
Lu, Zhi Hong
Goedegebuure, S. Peter
Gillanders, William E.
Curiel, David T.
Engineering a Novel Modular Adenoviral mRNA Delivery Platform Based on Tag/Catcher Bioconjugation
title Engineering a Novel Modular Adenoviral mRNA Delivery Platform Based on Tag/Catcher Bioconjugation
title_full Engineering a Novel Modular Adenoviral mRNA Delivery Platform Based on Tag/Catcher Bioconjugation
title_fullStr Engineering a Novel Modular Adenoviral mRNA Delivery Platform Based on Tag/Catcher Bioconjugation
title_full_unstemmed Engineering a Novel Modular Adenoviral mRNA Delivery Platform Based on Tag/Catcher Bioconjugation
title_short Engineering a Novel Modular Adenoviral mRNA Delivery Platform Based on Tag/Catcher Bioconjugation
title_sort engineering a novel modular adenoviral mrna delivery platform based on tag/catcher bioconjugation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674448/
https://www.ncbi.nlm.nih.gov/pubmed/38005953
http://dx.doi.org/10.3390/v15112277
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