Evidence map›Paper›PMID 32034124›Full record

ArticleNature communications2020

The COMET toolkit for composing customizable genetic programs in mammalian cells.

Patrick S Donahue, Joseph W Draut, Joseph J Muldoon, Hailey I Edelstein, Neda Bagheri, Joshua N Leonard

Abstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
–field-weighted citation impact
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

53 citing papers in PubMed.

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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

6 authors.

Patrick S DonahueDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, IL, 60208, USA.ORCID http://orcid.org/0000-0003-1415-6113
Joseph W Draut *Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL, 60208, USA.
Joseph J Muldoon *Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL, 60208, USA.ORCID http://orcid.org/0000-0003-3784-3565
Hailey I Edelstein *Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL, 60208, USA.ORCID http://orcid.org/0000-0002-8077-5492
Neda BagheriDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, IL, 60208, USA.ORCID http://orcid.org/0000-0003-0146-4627
Joshua N LeonardDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, IL, 60208, USA. j-leonard@northwestern.edu.ORCID http://orcid.org/0000-0003-4359-6126

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM008152 · NIGMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ARDEHALI, HOSSEIN · 1987 to 2021
$24.0M
Medical Scientist Training ProgramT32GM144295 · NIGMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ALAN R HAUSER · 2022 to 2026
$9.1M
Developing Capacity to Evaluate Training Programs via Development of Human, Institutional and Social CapitalT32GM008449 · NIGMS · NORTHWESTERN UNIVERSITY · PI LEONARD, JOSHUA NATHANIEL · 1993 to 2023
$7.8M
Design-driven engineering of robust mammalian sense-and-respond functions: from parts to programsR01EB026510 · NIBIB · NORTHWESTERN UNIVERSITY · PI Neda Bagheri, Joshua Nathaniel Leonard · 2018 to 2026
$3.7M
Therapeutic and Sustained Cytokine Delivery at the Tumor Site Using Engineered Mononuclear CellsF30CA203325 · NCI · NORTHWESTERN UNIVERSITY · PI DONAHUE, PATRICK SEAN · 2016 to 2019
$186k
NCI NIH HHS F30 CA203325NCI NIH HHS P30 CA060553NIBIB NIH HHS R01 EB026510NIGMS NIH HHS T32 GM008152NIGMS NIH HHS T32 GM008449NIGMS NIH HHS T32 GM144295
6 · The paper itself

Abstract

Engineering mammalian cells to carry out sophisticated and customizable genetic programs requires a toolkit of multiple orthogonal and well-characterized transcription factors (TFs). To address this need, we develop the COmposable Mammalian Elements of Transcription (COMET)-an ensemble of TFs and promoters that enable the design and tuning of gene expression to an extent not, to the best of our knowledge, previously possible. COMET currently comprises 44 activating and 12 inhibitory zinc-finger TFs and 83 cognate promoters, combined in a framework that readily accommodates new parts. This system can tune gene expression over three orders of magnitude, provides chemically inducible control of TF activity, and enables single-layer Boolean logic. We also develop a mathematical model that provides mechanistic insights into COMET performance characteristics. Altogether, COMET enables the design and construction of customizable genetic programs in mammalian cells.

Indexed as

Promoter Regions, GeneticAnimalsCell LineGenetic EngineeringHEK293 CellsHumansMammalsPlasmidsProtein EngineeringSmall Molecule LibrariesTranscription FactorsTranscription, GeneticZinc FingersSmall Molecule LibrariesTranscription Factors

Identifiers

PMID32034124
PMCPMC7005830

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.