Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Kexin Geng
ORCID logo ,
Paul J. Rice-Boucher
,
Elena A. Kashentseva
,
Igor P. Dmitriev
ORCID logo ,
Zhihong Lu
,
S. Peter Goedegebuure
,
William E. Gillanders
,
David T. Curiel
* ORCID logo
Version 1 : Received: 25 October 2023 / Approved: 25 October 2023 / Online: 25 October 2023 (10:31:41 CEST)

A peer-reviewed article of this Preprint also exists.

Geng, K.; Rice-Boucher, P.J.; Kashentseva, E.A.; Dmitriev, I.P.; Lu, Z.H.; Goedegebuure, S.P.; Gillanders, W.E.; Curiel, D.T. Engineering a Novel Modular Adenoviral mRNA Delivery Platform Based on Tag/Catcher Bioconjugation. Viruses 2023, 15, 2277. Geng, K.; Rice-Boucher, P.J.; Kashentseva, E.A.; Dmitriev, I.P.; Lu, Z.H.; Goedegebuure, S.P.; Gillanders, W.E.; Curiel, D.T. Engineering a Novel Modular Adenoviral mRNA Delivery Platform Based on Tag/Catcher Bioconjugation. Viruses 2023, 15, 2277.

Abstract

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, 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.

Keywords

mRNA delivery; adenovirus; Catcher/Tag bioconjugation; RNA binding protein; mRNA condensation; vaccine

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.