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@ARTICLE{Ketzer:127104,
      author       = {P. Ketzer$^*$ and J. K. Kaufmann$^*$ and S. Engelhardt$^*$
                      and S. Bossow$^*$ and C. von Kalle$^*$ and J. S. Hartig and
                      G. Ungerechts$^*$ and D. Nettelbeck$^*$},
      title        = {{A}rtificial riboswitches for gene expression and
                      replication control of {DNA} and {RNA} viruses.},
      journal      = {Proceedings of the National Academy of Sciences of the
                      United States of America},
      volume       = {111},
      number       = {5},
      issn         = {1091-6490},
      address      = {Washington, DC},
      publisher    = {National Acad. of Sciences},
      reportid     = {DKFZ-2017-03130},
      pages        = {E554 - E562},
      year         = {2014},
      abstract     = {Aptazymes are small, ligand-dependent self-cleaving
                      ribozymes that function independently of transcription
                      factors and can be customized for induction by various small
                      molecules. Here, we introduce these artificial riboswitches
                      for regulation of DNA and RNA viruses. We hypothesize that
                      they represent universally applicable tools for studying
                      viral gene functions and for applications as a safety switch
                      for oncolytic and live vaccine viruses. Our study shows that
                      the insertion of artificial aptazymes into the adenoviral
                      immediate early gene E1A enables small-molecule-triggered,
                      dose-dependent inhibition of gene expression.
                      Aptazyme-mediated shutdown of E1A expression translates into
                      inhibition of adenoviral genome replication, infectious
                      particle production, and cytotoxicity/oncolysis. These
                      results provide proof of concept for the aptazyme approach
                      for effective control of biological outcomes in eukaryotic
                      systems, specifically in virus infections. Importantly, we
                      also demonstrate aptazyme-dependent regulation of measles
                      virus fusion protein expression, translating into potent
                      reduction of progeny infectivity and virus spread. This not
                      only establishes functionality of aptazymes in fully
                      cytoplasmic genetic systems, but also implicates general
                      feasibility of this strategy for application in viruses with
                      either DNA or RNA genomes. Our study implies that gene
                      regulation by artificial riboswitches may be an appealing
                      alternative to Tet- and other protein-dependent gene
                      regulation systems, based on their small size, RNA-intrinsic
                      mode of action, and flexibility of the inducing molecule.
                      Future applications range from gene analysis in basic
                      research to medicine, for example as a safety switch for new
                      generations of efficiency-enhanced oncolytic viruses.},
      keywords     = {Adenovirus E1A Proteins (NLM Chemicals) / Ligands (NLM
                      Chemicals) / RNA, Catalytic (NLM Chemicals) / Riboswitch
                      (NLM Chemicals)},
      cin          = {F110 / G100},
      ddc          = {000},
      cid          = {I:(DE-He78)F110-20160331 / I:(DE-He78)G100-20160331},
      pnm          = {316 - Infections and cancer (POF3-316)},
      pid          = {G:(DE-HGF)POF3-316},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:24449891},
      pmc          = {pmc:PMC3918795},
      doi          = {10.1073/pnas.1318563111},
      url          = {https://inrepo02.dkfz.de/record/127104},
}