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Open AccessArticle

Arming Oncolytic Adenoviruses: Effect of Insertion Site and Splice Acceptor on Transgene Expression and Viral Fitness

1
ProCure Program, Institut Català d’Oncologia, and Oncobell Program IDIBELL, 08908 L’Hospitalet de Llobregat, Spain
2
VCN Biosciences S.L., 08174 Sant Cugat, Spain
3
Institut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Universitat de Barcelona, 08036 Barcelona, Spain
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(14), 5158; https://doi.org/10.3390/ijms21145158
Received: 2 July 2020 / Revised: 17 July 2020 / Accepted: 17 July 2020 / Published: 21 July 2020
(This article belongs to the Special Issue Adenovirus: Enduring Toolbox for Basic and Applied Research)
Oncolytic adenoviruses (OAds) present limited efficacy in clinics. The insertion of therapeutic transgenes into OAds genomes, known as “arming OAds”, has been the main strategy to improve their therapeutic potential. Different approaches were published in the decade of the 2000s, but with few comparisons. Most armed OAds have complete or partial E3 deletions, leading to a shorter half-life in vivo. We generated E3+ OAds using two insertion sites, After-fiber and After-E4, and two different splice acceptors linked to the major late promoter, either the Ad5 protein IIIa acceptor (IIIaSA) or the Ad40 long fiber acceptor (40SA). The highest transgene levels were obtained with the After-fiber location and 40SA. However, the set of codons of the transgene affected viral fitness, highlighting the relevance of transgene codon usage when arming OAds using the major late promoter. View Full-Text
Keywords: oncolytic adenovirus; adenovirus; transgenes; splice acceptor; codon usage oncolytic adenovirus; adenovirus; transgenes; splice acceptor; codon usage
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MDPI and ACS Style

Farrera-Sal, M.; de Sostoa, J.; Nuñez-Manchón, E.; Moreno, R.; Fillat, C.; Bazan-Peregrino, M.; Alemany, R. Arming Oncolytic Adenoviruses: Effect of Insertion Site and Splice Acceptor on Transgene Expression and Viral Fitness. Int. J. Mol. Sci. 2020, 21, 5158. https://doi.org/10.3390/ijms21145158

AMA Style

Farrera-Sal M, de Sostoa J, Nuñez-Manchón E, Moreno R, Fillat C, Bazan-Peregrino M, Alemany R. Arming Oncolytic Adenoviruses: Effect of Insertion Site and Splice Acceptor on Transgene Expression and Viral Fitness. International Journal of Molecular Sciences. 2020; 21(14):5158. https://doi.org/10.3390/ijms21145158

Chicago/Turabian Style

Farrera-Sal, Martí; de Sostoa, Jana; Nuñez-Manchón, Estela; Moreno, Rafael; Fillat, Cristina; Bazan-Peregrino, Miriam; Alemany, Ramon. 2020. "Arming Oncolytic Adenoviruses: Effect of Insertion Site and Splice Acceptor on Transgene Expression and Viral Fitness" Int. J. Mol. Sci. 21, no. 14: 5158. https://doi.org/10.3390/ijms21145158

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