Evidence map›Paper›PMID 28748410›Full record

ArticleMolecular biology reports2017

Cytotoxic effect of co-expression of human hepatitis A virus 3C protease and bifunctional suicide protein FCU1 genes in a bicistronic vector.

Alexey Komissarov, Ilya Demidyuk, Dina Safina, Marina Roschina, Andrey Shubin, Nataliya Lunina, Maria Karaseva, Sergey Kostrov

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Article in Molecular biology reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.3field-weighted citation impact, top 42% 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

4 citing papers in PubMed, 7 citations in OpenAlex.

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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

8 authors at 1 institution in 1 country.

Alexey KomissarovLaboratory of Protein Engineering, Institute of Molecular Genetics, Russian Academy of Science, 2 Kurchatova Sq., Moscow, Russia, 123182.
Ilya DemidyukLaboratory of Protein Engineering, Institute of Molecular Genetics, Russian Academy of Science, 2 Kurchatova Sq., Moscow, Russia, 123182. duk@img.ras.ru.ORCID http://orcid.org/0000-0001-8140-2287
Dina SafinaLaboratory of Protein Engineering, Institute of Molecular Genetics, Russian Academy of Science, 2 Kurchatova Sq., Moscow, Russia, 123182.
Marina RoschinaLaboratory of Protein Engineering, Institute of Molecular Genetics, Russian Academy of Science, 2 Kurchatova Sq., Moscow, Russia, 123182.
Andrey ShubinLaboratory of Protein Engineering, Institute of Molecular Genetics, Russian Academy of Science, 2 Kurchatova Sq., Moscow, Russia, 123182.
Nataliya LuninaLaboratory of Protein Engineering, Institute of Molecular Genetics, Russian Academy of Science, 2 Kurchatova Sq., Moscow, Russia, 123182.
Maria KarasevaLaboratory of Protein Engineering, Institute of Molecular Genetics, Russian Academy of Science, 2 Kurchatova Sq., Moscow, Russia, 123182.
Sergey KostrovLaboratory of Protein Engineering, Institute of Molecular Genetics, Russian Academy of Science, 2 Kurchatova Sq., Moscow, Russia, 123182.
Kurchatov Institute · RU

Funding

Russian Foundation for Basic Research 15-04-05169Russian Foundation for Basic Research 16-04-01048Russian Foundation for Basic Research (RU) 13-04-40172
6 · The paper itself

Abstract

Recent reports on various cancer models demonstrate a great potential of cytosine deaminase/5-fluorocytosine suicide system in cancer therapy. However, this approach has limited success and its application to patients has not reached the desirable clinical significance. Accordingly, the improvement of this suicide system is an actively developing trend in gene therapy. The purpose of this study was to explore the cytotoxic effect observed after co-expression of hepatitis A virus 3C protease (3C) and yeast cytosine deaminase/uracil phosphoribosyltransferase fusion protein (FCU1) in a bicistronic vector. A set of mono- and bicistronic plasmid constructs was generated to provide individual or combined expression of 3C and FCU1. The constructs were introduced into HEK293 and HeLa cells, and target protein synthesis as well as the effect of 5-fluorocytosine on cell death and the time course of the cytotoxic effect was studied. The obtained vectors provide for the synthesis of target proteins in human cells. The expression of the genes in a bicistronic construct provide for the cytotoxic effect comparable to that observed after the expression of genes in monocistronic constructs. At the same time, co-expression of FCU1 and 3C recapitulated their cytotoxic effects. The combined effect of the killer and suicide genes was studied for the first time on human cells in vitro. The integration of different gene therapy systems inducing cell death (FCU1 and 3C genes) in a bicistronic construct allowed us to demonstrate that it does not interfere with the cytotoxic effect of each of them. A combination of cytotoxic genes in multicistronic vectors can be used to develop pluripotent gene therapy agents.

Indexed as

3C Viral ProteasesCysteine EndopeptidasesCytosine DeaminaseFlucytosineGenes, Transgenic, SuicideGenetic TherapyGenetic VectorsHEK293 CellsHeLa CellsHepatitis A Virus, HumanHumansPentosyltransferasesPlasmidsProdrugsTransduction, GeneticViral Proteins3C Viral ProteasesCysteine EndopeptidasesCytosine DeaminaseFlucytosinePentosyltransferasesProdrugsuracil phosphoribosyltransferaseViral Proteins2A peptideBicistronic expression vectorCaspase-independent cell deathHuman hepatitis A virus 3C proteaseSuicide gene therapyYeast cytosine deaminase/uracil phosphoribosyltransferase fusion gene

Identifiers

PMID28748410
OpenAlexW2736334581

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Registered trials

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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.