Arming Oncolytic Adenoviruses: Effect of Insertion Site and Splice Acceptor on Transgene Expression and Viral Fitness
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 compar...
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| Format: | Article |
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MDPI AG
2020-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/14/5158 |
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| author | Martí Farrera-Sal Jana de Sostoa Estela Nuñez-Manchón Rafael Moreno Cristina Fillat Miriam Bazan-Peregrino Ramon Alemany |
| author_facet | Martí Farrera-Sal Jana de Sostoa Estela Nuñez-Manchón Rafael Moreno Cristina Fillat Miriam Bazan-Peregrino Ramon Alemany |
| author_sort | Martí Farrera-Sal |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T18:20:17Z |
| format | Article |
| id | doaj.art-de756b9792de4753b1de4ed92bb6fca6 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:20:17Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-de756b9792de4753b1de4ed92bb6fca62023-11-20T07:26:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012114515810.3390/ijms21145158Arming Oncolytic Adenoviruses: Effect of Insertion Site and Splice Acceptor on Transgene Expression and Viral FitnessMartí Farrera-Sal0Jana de Sostoa1Estela Nuñez-Manchón2Rafael Moreno3Cristina Fillat4Miriam Bazan-Peregrino5Ramon Alemany6ProCure Program, Institut Català d’Oncologia, and Oncobell Program IDIBELL, 08908 L’Hospitalet de Llobregat, SpainProCure Program, Institut Català d’Oncologia, and Oncobell Program IDIBELL, 08908 L’Hospitalet de Llobregat, SpainInstitut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Universitat de Barcelona, 08036 Barcelona, SpainProCure Program, Institut Català d’Oncologia, and Oncobell Program IDIBELL, 08908 L’Hospitalet de Llobregat, SpainInstitut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Universitat de Barcelona, 08036 Barcelona, SpainVCN Biosciences S.L., 08174 Sant Cugat, SpainProCure Program, Institut Català d’Oncologia, and Oncobell Program IDIBELL, 08908 L’Hospitalet de Llobregat, SpainOncolytic 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.https://www.mdpi.com/1422-0067/21/14/5158oncolytic adenovirusadenovirustransgenessplice acceptorcodon usage |
| spellingShingle | Martí Farrera-Sal Jana de Sostoa Estela Nuñez-Manchón Rafael Moreno Cristina Fillat Miriam Bazan-Peregrino Ramon Alemany Arming Oncolytic Adenoviruses: Effect of Insertion Site and Splice Acceptor on Transgene Expression and Viral Fitness International Journal of Molecular Sciences oncolytic adenovirus adenovirus transgenes splice acceptor codon usage |
| title | Arming Oncolytic Adenoviruses: Effect of Insertion Site and Splice Acceptor on Transgene Expression and Viral Fitness |
| title_full | Arming Oncolytic Adenoviruses: Effect of Insertion Site and Splice Acceptor on Transgene Expression and Viral Fitness |
| title_fullStr | Arming Oncolytic Adenoviruses: Effect of Insertion Site and Splice Acceptor on Transgene Expression and Viral Fitness |
| title_full_unstemmed | Arming Oncolytic Adenoviruses: Effect of Insertion Site and Splice Acceptor on Transgene Expression and Viral Fitness |
| title_short | Arming Oncolytic Adenoviruses: Effect of Insertion Site and Splice Acceptor on Transgene Expression and Viral Fitness |
| title_sort | arming oncolytic adenoviruses effect of insertion site and splice acceptor on transgene expression and viral fitness |
| topic | oncolytic adenovirus adenovirus transgenes splice acceptor codon usage |
| url | https://www.mdpi.com/1422-0067/21/14/5158 |
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