Evidence map›Paper›PMID 23349911›Full record

ArticlePloS one2013

MicroRNA-mediated suppression of oncolytic adenovirus replication in human liver.

Erkko Ylösmäki, Sergio Lavilla-Alonso, Sari Jäämaa, Markus Vähä-Koskela, Taija af Hällström, Akseli Hemminki, Johanna Arola, Heikki Mäkisalo, Kalle Saksela

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
5.3field-weighted citation impact, top 4% 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

19 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Impact of Autophagy in Oncolytic Adenoviral Therapy for Cancer.International journal of molecular sciences · 2017
    Review
  6. Oncolytic virotherapy for urological cancers.Nature reviews. Urology · 2016
    Review
  7. MicroRNA-regulated viral vectors for gene therapy.World journal of experimental medicine · 2016
    Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Review
  18. Article
  19. Review
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

9 authors at 2 institutions in 1 country.

Erkko YlösmäkiDepartment of Virology, Haartman Institute, University of Helsinki and HUSLAB, Helsinki University Central Hospital, Helsinki, Finland.
Sergio Lavilla-Alonso
Sari Jäämaa
Markus Vähä-Koskela
Taija af Hällström
Akseli Hemminki
Johanna Arola
Heikki Mäkisalo
Kalle Saksela
University of Helsinki · FIHelsinki University Hospital · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

MicroRNAs (miRNAs) are important and ubiquitous regulators of gene expression that can suppress their target genes by translational inhibition as well as mRNA destruction. Cell type-specific miRNA expression patterns have been successfully exploited for targeting the expression of experimental and therapeutic gene constructs, for example to reduce pathogenic effects of cancer virotherapy in normal tissues. In order to avoid liver damage associated with systemic or intrahepatic delivery of oncolytic adenoviruses we have introduced the concept of suppressing adenovirus replication in hepatic cells by inserting target elements for the liver-specific miR122 into the viral genome. Here we show using ex vivo cultured tissue specimens that six perfectly complementary miR122 target sites in the 3' untranslated region of the viral E1A gene are sufficient in the absence of any other genetic modifications to prevent productive replication of serotype 5 adenovirus (Ad5) in normal human liver. This modification did not compromise the replicative capacity of the modified virus in cancer tissue derived from a colon carcinoma liver metastasis or its oncolytic potency in a human lung cancer xenograft mouse model. Unlike wild-type Ad5, the modified virus did not result in increased serum levels of liver enzymes in infected mice. These results provide a strong preclinical proof of concept for the use of miR122 target sites for reducing the risk of liver damage caused by oncolytic adenoviruses, and suggest that ectopic miR122 target elements should be considered as an additional safety measure included in any therapeutic virus or viral vector posing potential hazard to the liver.

Indexed as

Genetic TherapyAdenoviridaeAdenovirus E1A ProteinsAnimalsColonic NeoplasmsGene Expression RegulationGenome, ViralHumansLiverLung NeoplasmsMiceMicroRNAsNeoplasm MetastasisOncolytic VirusesOrgan SpecificityTransplantation, HeterologousAdenovirus E1A ProteinsMicroRNAs

Identifiers

PMID23349911
PMCPMC3551754
OpenAlexW2008631030

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.