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The revolving door of adenovirus cell entry: not all pathways are equal

Nestic, Davor, Bozinovic, Ksenija, Pehar, Isabela, Wallace, Rebecca, Parker, Alan L. and Majhen, Dragomira 2021. The revolving door of adenovirus cell entry: not all pathways are equal. Pharmaceutics 13 (10) , 1585. 10.3390/pharmaceutics13101585

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Abstract

Adenoviruses represent exceptional candidates for wide-ranging therapeutic applications, from vectors for gene therapy to oncolytics for cancer treatments. The first ever commercial gene therapy medicine was based on a recombinant adenovirus vector, while most recently, adenoviral vectors have proven critical as vaccine platforms in effectively controlling the global coronavirus pandemic. Here, we discuss factors involved in adenovirus cell binding, entry, and trafficking; how they influence efficiency of adenovirus-based vectors; and how they can be manipulated to enhance efficacy of genetically modified adenoviral variants. We focus particularly on endocytosis and how different adenovirus serotypes employ different endocytic pathways to gain cell entry, and thus, have different intracellular trafficking pathways that subsequently trigger different host antiviral responses. In the context of gene therapy, the final goal of the adenovirus vector is to efficiently deliver therapeutic transgenes into the target cell nucleus, thus allowing its functional expression. Aberrant or inefficient endocytosis can impede this goal, therefore, it should be considered when designing and constructing adenovirus-based vectors.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: 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/)
Publisher: MDPI
ISSN: 1999-4923
Funders: Cancer Research UK
Date of First Compliant Deposit: 30 September 2021
Date of Acceptance: 24 September 2021
Last Modified: 04 Oct 2021 09:59
URI: http://orca.cardiff.ac.uk/id/eprint/144557

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