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Title: Arming Oncolytic Adenoviruses: Effect of Insertion Site and Splice Acceptor on Transgene Expression and Viral Fitness
Author: Farrera Sal, Martí
Sostoa, Jana de
Nuñez Manchón, Estela
Moreno Olié, Rafael
Fillat i Fonts, Cristina
Bazan Peregrino, Miriam
Alemany Bonastre, Ramon
Keywords: Adenovirus
Enginyeria genètica
Genetic engineering
Issue Date: 1-Jul-2020
Publisher: MDPI
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: International Journal of Molecular Sciences, 2020, vol. 21, num. 14
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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