Evidence map›Paper›PMID 30778069›Full record

ArticleNature communications2019

Precise tuning of gene expression levels in mammalian cells.

Yale S Michaels, Mike B Barnkob, Hector Barbosa, Toni A Baeumler, Mary K Thompson, Violaine Andre, Huw Colin-York, Marco Fritzsche, Uzi Gileadi, Hilary M Sheppard and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

40 citing papers in PubMed, 70 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

14 authors at 3 institutions in 2 countries.

Yale S MichaelsWeatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.ORCID http://orcid.org/0000-0002-6857-5922
Mike B BarnkobMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine University of Oxford, Oxford, OX3 9DS, UK.ORCID http://orcid.org/0000-0002-5892-1174
Hector BarbosaWeatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Toni A BaeumlerWeatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Mary K ThompsonDepartment of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.ORCID http://orcid.org/0000-0002-4947-6048
Violaine AndreMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine University of Oxford, Oxford, OX3 9DS, UK.
Huw Colin-YorkMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine University of Oxford, Oxford, OX3 9DS, UK.
Marco FritzscheMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine University of Oxford, Oxford, OX3 9DS, UK.
Uzi GileadiMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine University of Oxford, Oxford, OX3 9DS, UK.
Hilary M SheppardSchool of Biological Sciences, University of Auckland, Auckland, 1050, New Zealand.
David J H F KnappWeatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Thomas A MilneWeatherall Institute of Molecular Medicine, MRC Molecular Haematology Unit, NIHR Oxford Biomedical Research Centre Programme, University of Oxford, Oxford, OX3 9DS, UK.ORCID http://orcid.org/0000-0002-0413-4271
Vincenzo CerundoloMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine University of Oxford, Oxford, OX3 9DS, UK.
Tudor A FulgaWeatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK. tudor.fulga@imm.ox.ac.uk.
University of Oxford · GBNuffield Orthopaedic Centre · GBUniversity of Auckland · NZ

Funding

Medical Research Council G0902418Medical Research Council MC_UU_00008/1Medical Research Council MC_UU_00016/6Medical Research Council MC_UU_12009/6
6 · The paper itself

Abstract

Precise, analogue regulation of gene expression is critical for cellular function in mammals. In contrast, widely employed experimental and therapeutic approaches such as knock-in/out strategies are more suitable for binary control of gene activity. Here we report on a method for precise control of gene expression levels in mammalian cells using engineered microRNA response elements (MREs). First, we measure the efficacy of thousands of synthetic MRE variants under the control of an endogenous microRNA by high-throughput sequencing. Guided by this data, we establish a library of microRNA silencing-mediated fine-tuners (miSFITs) of varying strength that can be employed to precisely control the expression of user-specified genes. We apply this technology to tune the T-cell co-inhibitory receptor PD-1 and to explore how antigen expression influences T-cell activation and tumour growth. Finally, we employ CRISPR/Cas9 mediated homology directed repair to introduce miSFITs into the BRCA1 3'UTR, demonstrating that this versatile tool can be used to tune endogenous genes.

Indexed as

Genetic TechniquesResponse Elements3' Untranslated RegionsAnimalsB7-H1 AntigenCRISPR-Cas SystemsGene Expression RegulationGenes, BRCA1HEK293 CellsHigh-Throughput Nucleotide SequencingHumansMelanoma, ExperimentalMice, Inbred C57BLMicroRNAsOvalbuminRecombinant Proteins3' Untranslated RegionsB7-H1 AntigenCD274 protein, humanMicroRNAsOvalbuminRecombinant Proteins

Identifiers

PMID30778069
PMCPMC6379387
OpenAlexW2913124665

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.