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The Revolving Door of Adenovirus Cell Entry: Not All Pathways Are Equal

Division of Molecular Biology, Ruđer Bošković Institute, 10000 Zagreb, Croatia
Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK
Author to whom correspondence should be addressed.
Equal contribution.
Academic Editor: Imran Saleem
Pharmaceutics 2021, 13(10), 1585;
Received: 28 August 2021 / Revised: 23 September 2021 / Accepted: 24 September 2021 / Published: 29 September 2021
(This article belongs to the Special Issue Advanced Use of Adenoviral Vectors in Cancer and Gene Therapy)
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. View Full-Text
Keywords: adenovirus; endocytosis; vectors; gene therapy adenovirus; endocytosis; vectors; gene therapy
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MDPI and ACS Style

Nestić, D.; Božinović, K.; Pehar, I.; Wallace, R.; Parker, A.L.; Majhen, D. The Revolving Door of Adenovirus Cell Entry: Not All Pathways Are Equal. Pharmaceutics 2021, 13, 1585.

AMA Style

Nestić D, Božinović K, Pehar I, Wallace R, Parker AL, Majhen D. The Revolving Door of Adenovirus Cell Entry: Not All Pathways Are Equal. Pharmaceutics. 2021; 13(10):1585.

Chicago/Turabian Style

Nestić, Davor, Ksenija Božinović, Isabela Pehar, Rebecca Wallace, Alan L. Parker, and Dragomira Majhen. 2021. "The Revolving Door of Adenovirus Cell Entry: Not All Pathways Are Equal" Pharmaceutics 13, no. 10: 1585.

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