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

Lade...
Vorschaubild
Dateien
ketzer_211505.pdf
ketzer_211505.pdfGröße: 4.48 MBDownloads: 631
Datum
2012
Autor:innen
Ketzer, Patrick
Haas, Simon F.
Engelhardt, Sarah
Nettelbeck, Dirk M.
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
DOI (zitierfähiger Link)
ArXiv-ID
Internationale Patentnummer
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Open Access Green
Sammlungen
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
Nucleic Acids Research. 2012, 40(21), pp. e167-e167. ISSN 0305-1048. eISSN 1362-4962. Available under: doi: 10.1093/nar/gks734
Zusammenfassung

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.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
540 Chemie
Schlagwörter
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690KETZER, 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. 2012, 40(21), pp. e167-e167. ISSN 0305-1048. eISSN 1362-4962. Available under: doi: 10.1093/nar/gks734
BibTex
@article{Ketzer2012-11Synth-21150,
  year={2012},
  doi={10.1093/nar/gks734},
  title={Synthetic riboswitches for external regulation of genes transferred by replication-deficient and oncolytic adenoviruses},
  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: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/server/rdf/resource/123456789/21150">
    <dc:contributor>Nettelbeck, Dirk M.</dc:contributor>
    <dc:contributor>Engelhardt, Sarah</dc:contributor>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/21150/2/ketzer_211505.pdf"/>
    <dc:contributor>Haas, Simon F.</dc:contributor>
    <dc:language>eng</dc:language>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/>
    <dc:creator>Hartig, Jörg S.</dc:creator>
    <dc:contributor>Ketzer, Patrick</dc:contributor>
    <dcterms:bibliographicCitation>Nucleic Acids Research ; 40 (2012), 21. - e167</dcterms:bibliographicCitation>
    <dc:creator>Nettelbeck, Dirk M.</dc:creator>
    <dc:creator>Engelhardt, Sarah</dc:creator>
    <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/21150"/>
    <dcterms:issued>2012-11</dcterms:issued>
    <dc:creator>Ketzer, Patrick</dc:creator>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2013-01-25T10:56:11Z</dcterms:available>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/29"/>
    <dc:contributor>Hartig, Jörg S.</dc:contributor>
    <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>
    <dc:creator>Haas, Simon F.</dc:creator>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/21150/2/ketzer_211505.pdf"/>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/29"/>
    <dcterms:title>Synthetic riboswitches for external regulation of genes transferred by replication-deficient and oncolytic adenoviruses</dcterms:title>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2013-01-25T10:56:11Z</dc:date>
    <dc:rights>terms-of-use</dc:rights>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
  </rdf:Description>
</rdf:RDF>
Interner Vermerk
xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter
Kontakt
URL der Originalveröffentl.
Prüfdatum der URL
Prüfungsdatum der Dissertation
Finanzierungsart
Kommentar zur Publikation
Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Ja
Begutachtet
Diese Publikation teilen