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

Autor: Kexin Geng, Paul J. Rice-Boucher, Elena A. Kashentseva, Igor P. Dmitriev, Zhi Hong Lu, S. Peter Goedegebuure, William E. Gillanders, David T. Curiel
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Viruses, Vol 15, Iss 11, p 2277 (2023)
Druh dokumentu: article
ISSN: 1999-4915
DOI: 10.3390/v15112277
Popis: 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.
Databáze: Directory of Open Access Journals
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