Evidence map›Paper›PMID 24449891›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Artificial riboswitches for gene expression and replication control of DNA and RNA viruses.

Patrick Ketzer, Johanna K Kaufmann, Sarah Engelhardt, Sascha Bossow, Christof von Kalle, Jörg S Hartig, Guy Ungerechts, Dirk M Nettelbeck

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
6.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 113 citations in OpenAlex.

  1. Review
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  8. Human Synthetic Biology and Programmable Gene Regulation Control.Annual review of genomics and human genetics · 2025
    Review
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  20. Viral Replicon Systems and Their Biosafety Aspects.Applied biosafety : journal of the American Biological Safety Association · 2023
    Review

2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 1 country.

Patrick KetzerOncolytic Adenovirus Group, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), 69120 Heidelberg, Germany.
Johanna K Kaufmann
Sarah Engelhardt
Sascha Bossow
Christof von Kalle
Jörg S Hartig
Guy Ungerechts
Dirk M Nettelbeck
Heidelberg University · DEGerman Cancer Research Center · DEUniversity Hospital Heidelberg · DEUniversity of Konstanz · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Gene Expression Regulation, ViralAdenoviridaeAdenovirus E1A ProteinsCell LineDNA VirusesGenes, ViralLigandsMeasles virusOncolytic VirusesRiboswitchRNA, CatalyticRNA VirusesVirionVirus InternalizationVirus ReplicationAdenovirus E1A ProteinsLigandsRiboswitchRNA, Catalytic

Identifiers

PMID24449891
PMCPMC3918795
OpenAlexW2141553824

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.