Evidence map›Paper›PMID 22885302›Full record

ArticleNucleic acids research2012

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

Patrick Ketzer, Simon F Haas, Sarah Engelhardt, Jörg S Hartig, Dirk M Nettelbeck

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

34 citing papers in PubMed, 63 citations in OpenAlex.

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  19. Biomedical Applications of RNA-Based Devices.Current opinion in biomedical engineering · 2017
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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

5 authors at 4 institutions in 1 country.

Patrick KetzerHelmholtz-University Group Oncolytic Adenoviruses, Deutsches Krebsforschungszentrum (DKFZ, German Cancer Research Center) and Department of Dermatology, Heidelberg University Hospital, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.
Simon F Haas
Sarah Engelhardt
Jörg S Hartig
Dirk M Nettelbeck
University Hospital Heidelberg · DEGerman Cancer Research Center · DEHeidelberg University · DEUniversity of Konstanz · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Gene Expression RegulationRiboswitchAdenoviridaeCell Line, TumorDefective VirusesDependovirusGenetic VectorsGenome, ViralHumansOncolytic VirusesRNA, CatalyticTransduction, GeneticTransgenesUntranslated RegionsVirus ReplicationRiboswitchRNA, CatalyticUntranslated Regions

Identifiers

PMID22885302
PMCPMC3505972
OpenAlexW2058905055

What OpenQuestion holds

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LicenceCC BY-NC
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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.