Transduction Properties of an Adenovirus Vector Containing Sequences Complementary to a Liver-Specific microRNA, miR-122a, in the 3′-Untranslated Region of the E4 Gene in Human Hepatocytes from Chimeric Mice with Humanized Liver
Rattachement africain : fr, jp. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Replication-incompetent adenovirus (Ad) vectors are promising gene delivery vehicles, especially for hepatocytes, due to their superior hepatic tropism; however, in vivo application of an Ad vector often results in hepatotoxicity, mainly due to the leaky expression of Ad genes from the Ad vector genome. In order to reduce the Ad vector-induced hepatotoxicity, we previously developed an Ad vector containing the sequences perfectly complementary to a liver-specific microRNA (miRNA), miR-122a, in the 3'-untranslated region (UTR) of the E4 gene. This improved Ad vector showed a significant reduction in the leaky expression of Ad genes and hepatotoxicity in the mouse liver and primary mouse hepatocytes; however, the safety profiles and transduction properties of this improved Ad vector in human hepatocytes remained to be elucidated. In this study, we examined the transgene expression and safety profiles of Ad vectors with miR-122a-targeted sequences in the 3'-UTR of the E4 gene in human hepatocytes from chimeric mice with humanized liver. The transgene expression levels of Ad vectors with miR-122a-targeted sequences in the 3'-UTR of the E4 gene were significantly higher than those of the conventional Ad vectors. The leaky expression levels of Ad genes of Ad vectors with miR-122a-targeted sequences in the 3'-UTR of the E4 gene in the primary human hepatocytes were largely reduced, compared with the conventional Ad vectors, resulting in an improvement in Ad vector-induced cytotoxicity. These data indicated that this improved Ad vector was a superior gene delivery vehicle without severe cytotoxicity for not only mouse hepatocytes but also human hepatocytes.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Transduction Properties of an Adenovirus Vector Containing Sequences Complementary to a Liver-Specific microRNA, miR-122a, in the 3′-Untranslated Region of the E4 Gene in Human Hepatocytes from Chimeric Mice with Humanized Liver
- Date Crossref
- 01/10/2021
- Éditeur
- Pharmaceutical Society of Japan
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Laboratoire de Biochimie pays non établi dans la noticeStructure de recherche
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The University of Osaka pays non établi dans la noticeUniversité ou école supérieure
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Hiroshima University Collaborative Research Laboratory of Medical Innovation pays non établi dans la noticeUniversité ou école supérieure
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PhoenixBio (Japan) pays non établi dans la noticeEntreprise
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RIKEN Center for Integrative Medical Sciences pays non établi dans la noticeStructure de recherche
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National Institute of Biomedical Innovation pays non établi dans la noticeStructure de recherche
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Graduate School of Pharmaceutical Sciences Laboratory of Biochemistry and Molecular Biology pays non établi dans la noticeUniversité ou école supérieure
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Ltd PhoenixBio Co. pays non établi dans la noticeEntreprise
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Osaka University Global Center for Medical Engineering and Informatics pays non établi dans la noticeUniversité ou école supérieure
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Laboratory of Hepatocyte Regulation pays non établi dans la noticeStructure de recherche
Laboratoire de Biochimie, The University of Osaka et Collaborative Research Laboratory of Medical Innovation — Hiroshima University, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.