Evidence map›Paper›PMID 25849659›Full record

ArticlePloS one2015

Chromatin function modifying elements in an industrial antibody production platform--comparison of UCOE, MAR, STAR and cHS4 elements.

Fay Saunders, Berni Sweeney, Michael N Antoniou, Paul Stephens, Katharine Cain

Open access · goldAbstract readComparative Study
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

35 citing papers in PubMed, 83 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

5 authors at 1 institution in 1 country.

Fay SaundersProtein Expression and Purification Group, UCB, Slough, Berkshire, United Kingdom.
Berni SweeneyProtein Expression and Purification Group, UCB, Slough, Berkshire, United Kingdom.
Michael N AntoniouGene Expression and Therapy Group, King's College School of Medicine, Department of Molecular Genetics, Guy's Hospital, London Bridge, London, United Kingdom.
Paul StephensProtein Expression and Purification Group, UCB, Slough, Berkshire, United Kingdom.
Katharine CainProtein Expression and Purification Group, UCB, Slough, Berkshire, United Kingdom.
Guy's Hospital · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The isolation of stably transfected cell lines suitable for the manufacture of biotherapeutic protein products can be an arduous process relying on the identification of a high expressing clone; this frequently involves transgene amplification and maintenance of the clones' expression over at least 60 generations. Maintenance of expression, or cell line stability, is highly dependent upon the nature of the genomic environment at the site of transgene integration, where epigenetic mechanisms lead to variable expression and silencing in the vast majority of cases. We have assessed four chromatin function modifying elements (A2UCOE, MAR X_S29, STAR40 and cHS4) for their ability to negate chromatin insertion site position effects and their ability to express and maintain monoclonal antibody expression. Each element was analysed by insertion into different positions within a vector, either flanking or between heavy chain (HC) and light chain (LC) antibody expression cassettes. Our results clearly show that the A2UCOE is the most beneficial element in this system, with stable cell pools and clones increasing antibody yields 6.5-fold and 6.75-fold respectively. Stability analysis demonstrated that the reduction in antibody expression, seen with cells transfected with the control vector over 120 generations, was mitigated in the clones containing A2UCOE-augmented transgenes. Analysis also showed that the A2UCOE reduced the amount of transgene promoter DNA methylation, which contributed to the maintenance of starting levels of expression.

Indexed as

AnimalsAntibody FormationCHO CellsChromatinChromosomal Proteins, Non-HistoneCricetulusDNA MethylationEpigenesis, GeneticGene SilencingGenetic VectorsHumansImmunoglobulin Heavy ChainsImmunoglobulin Light ChainsIn Situ Hybridization, FluorescenceMicePromoter Regions, GeneticChromatinChromosomal Proteins, Non-HistoneImmunoglobulin Heavy ChainsImmunoglobulin Light Chains

Identifiers

PMID25849659
PMCPMC4388700
OpenAlexW2061738853

What OpenQuestion holds

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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.