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• W2058905055 endingPage "e167" @default.
• W2058905055 startingPage "e167" @default.
• W2058905055 abstract "Therapeutic gene transfer by replication-defective viral vectors or, for cancer treatment, by replication-competent oncolytic viruses shows high promise for treatment of major diseases. To ensure safety, timing or dosing in patients, external control of therapeutic gene expression is desirable or even required. In this study, we explored the potential of artificial aptazymes, ligand-dependent self-cleaving ribozymes, as an innovative tool for regulation of therapeutic gene expression. Importantly, aptazymes act on RNA intrinsically, independent of regulatory protein–nucleic acid interactions and stoichiometry, are non-immunogenic and of small size. These are key advantages compared with the widely used inducible promoters, which were also reported to lose regulation at high copy numbers, e.g. after replication of oncolytic viruses. We characterized aptazymes in therapeutic gene transfer utilizing adenovectors (AdVs), adeno-associated vectors (AAVs) and oncolytic adenoviruses (OAds), which are all in advanced clinical testing. Our results show similar aptazyme-mediated regulation of gene expression by plasmids, AdVs, AAVs and OAds. Insertion into the 5′-, 3′- or both untranslated regions of several transgenes resulted in ligand-responsive gene expression. Notably, aptazyme regulation was retained during OAd replication and spread. In conclusion, our study demonstrates the fidelity of aptazymes in viral vectors and oncolytic viruses and highlights the potency of riboswitches for medical applications." @default.
• W2058905055 created "2016-06-24" @default.
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• W2058905055 date "2012-08-09" @default.
• W2058905055 modified "2023-10-12" @default.
• W2058905055 title "Synthetic riboswitches for external regulation of genes transferred by replication-deficient and oncolytic adenoviruses" @default.
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• W2058905055 doi "https://doi.org/10.1093/nar/gks734" @default.
• W2058905055 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3505972" @default.
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