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Synthetic riboswitches for external regulation of genes transferred by replication-deficient and oncolytic adenoviruses

Synthetic riboswitches for external regulation of genes transferred by replication-deficient and oncolytic adenoviruses

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KETZER, Patrick, Simon F. HAAS, Sarah ENGELHARDT, Jörg S. HARTIG, Dirk M. NETTELBECK, 2012. Synthetic riboswitches for external regulation of genes transferred by replication-deficient and oncolytic adenoviruses. In: Nucleic Acids Research. 40(21), pp. e167-e167. ISSN 0305-1048. eISSN 1362-4962. Available under: doi: 10.1093/nar/gks734

@article{Ketzer2012-11Synth-21150, title={Synthetic riboswitches for external regulation of genes transferred by replication-deficient and oncolytic adenoviruses}, year={2012}, doi={10.1093/nar/gks734}, number={21}, volume={40}, issn={0305-1048}, journal={Nucleic Acids Research}, pages={e167--e167}, author={Ketzer, Patrick and Haas, Simon F. and Engelhardt, Sarah and Hartig, Jörg S. and Nettelbeck, Dirk M.} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/21150"> <dcterms:abstract xml:lang="eng">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.</dcterms:abstract> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/21150"/> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2013-01-25T10:56:11Z</dcterms:available> <dc:rights>terms-of-use</dc:rights> <dc:contributor>Hartig, Jörg S.</dc:contributor> <dcterms:bibliographicCitation>Nucleic Acids Research ; 40 (2012), 21. - e167</dcterms:bibliographicCitation> <dc:contributor>Ketzer, Patrick</dc:contributor> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/29"/> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/21150/2/ketzer_211505.pdf"/> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2013-01-25T10:56:11Z</dc:date> <dc:contributor>Engelhardt, Sarah</dc:contributor> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/29"/> <dc:contributor>Haas, Simon F.</dc:contributor> <dc:creator>Engelhardt, Sarah</dc:creator> <dcterms:issued>2012-11</dcterms:issued> <dc:language>eng</dc:language> <dcterms:rights rdf:resource="https://kops.uni-konstanz.de/page/termsofuse"/> <dc:contributor>Nettelbeck, Dirk M.</dc:contributor> <dc:creator>Ketzer, Patrick</dc:creator> <dc:creator>Hartig, Jörg S.</dc:creator> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/21150/2/ketzer_211505.pdf"/> <dcterms:title>Synthetic riboswitches for external regulation of genes transferred by replication-deficient and oncolytic adenoviruses</dcterms:title> <dc:creator>Nettelbeck, Dirk M.</dc:creator> <dc:creator>Haas, Simon F.</dc:creator> </rdf:Description> </rdf:RDF>

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