Evidence map›Paper›PMID 35132245›Full record

ArticleNature methods2022

NTR 2.0: a rationally engineered prodrug-converting enzyme with substantially enhanced efficacy for targeted cell ablation.

Abigail V Sharrock, Timothy S Mulligan, Kelsi R Hall, Elsie M Williams, David T White, Liyun Zhang, Kevin Emmerich, Frazer Matthews, Saumya Nimmagadda, Selena Washington and 11 more

Open access · greenAbstract read
In one paragraph

Article in Nature methods, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
9.1field-weighted citation impact, top 1% 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

54 citing papers in PubMed, 76 citations in OpenAlex.

  1. Article
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  6. Review
  7. Article
  8. Mesenchymal-derived neural progenitors underlie localbioRxiv : the preprint server for biology · 2026
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  10. A genetic reporter for visualizing nitroreductase activity using magnetic resonance imaging.Chemistry methods : new approaches to solving problems in chemistry · 2026
    Article
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  12. Hb-EGF directs systemic muscle repair.Development (Cambridge, England) · 2026
    Article
  13. Article
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  15. Article
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  17. Article
  18. Article
  19. Article
  20. Retinal Degeneration and Regeneration in Xenopus laevis Tadpoles.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
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

21 authors at 3 institutions in 2 countries.

Abigail V Sharrock *School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.ORCID http://orcid.org/0000-0003-2837-9481
Timothy S Mulligan *Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA.
Kelsi R HallSchool of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
Elsie M WilliamsSchool of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
David T WhiteDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA.
Liyun ZhangDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA.
Kevin EmmerichDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA.
Frazer MatthewsDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA.
Saumya NimmagaddaDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA.
Selena WashingtonDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA.
Katherine D LeDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA.
Danielle Meir-LeviDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA.
Olivia L CoxDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA.
Meera T SaxenaDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA.
Anne L CalofDepartment of Anatomy and Neurobiology, University of California, Irvine, CA, USA.
Martha E Lopez-BurksDepartment of Developmental and Cell Biology, University of California, Irvine, CA, USA.
Arthur D LanderDepartment of Developmental and Cell Biology, University of California, Irvine, CA, USA.ORCID http://orcid.org/0000-0002-4380-5525
Ding DingDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Hongkai JiDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-6480-0141
David F AckerleySchool of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand. david.ackerley@vuw.ac.nz.ORCID http://orcid.org/0000-0002-6188-9902
Jeff S MummDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA. jmumm3@jhmi.edu.ORCID http://orcid.org/0000-0002-2575-287X
Johns Hopkins University · USVictoria University of Wellington · NZUniversity of California, Irvine · US

Funding

Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Jiang Qian · 1985 to 2026
$22.1M
Visual Science Training ProgramT32EY007143 · NEI · JOHNS HOPKINS UNIVERSITY · PI Laura Ensign, JEREMY NATHANS · 1995 to 2026
$6.2M
Multiscale Models of Wound Cell Plasticity for RegenerationU01AR073159 · NIAMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI DAI, XING, NIE, QING · 2018 to 2022
$3.5M
Investigating the multifactorial origins of congenital heart diseaseR01HL138659 · NHLBI · UNIVERSITY OF CALIFORNIA-IRVINE · PI CALOF, ANNE LEIGHTON, LANDER, ARTHUR D · 2017 to 2020
$2.1M
Spatial Dynamics of Tissue and Organ Size ControlR01NS095355 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI CALOF, ANNE LEIGHTON, LANDER, ARTHUR D · 2015 to 2019
$2.1M
Novel models of Alzheimer's Disease and Related Disorders enabling systematic investigation of the therapeutic potential of transplanted hiPSC-derived cells and endogenous adult neural stem cellsR01OD020376 · OD · JOHNS HOPKINS UNIVERSITY · PI MUMM, JEFFREY · 2016 to 2020
$2.1M
Big Data Methods for Decoding Gene RegulationR01HG009518 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI JI, HONGKAI · 2018 to 2021
$1.7M
Robotic whole organism HTS platform for drug discovery and developmentR41TR000945 · NCATS · LUMINOMICS, INC. · PI MUMM, JEFFREY · 2014 to 2014
$225k
Identification of Cellular, Molecular and Genetic Factors Regulating RGC RegenerationF31EY032790 · NEI · JOHNS HOPKINS UNIVERSITY · PI EMMERICH, KEVIN · 2021 to 2024
$112k
Targeted Cellular Ablation in Transgenic ZebrafishR43HD047089 · NICHD · LUMINOMICS, INC. · PI MUMM, JEFFREY S. · 2004 to 2004
$107k
NCATS NIH HHS R41 TR000945NEI NIH HHS F31 EY032790NEI NIH HHS P30 EY001765NEI NIH HHS T32 EY007143NHGRI NIH HHS R01 HG009518NHLBI NIH HHS R01 HL138659NIAMS NIH HHS U01 AR073159NICHD NIH HHS R43 HD047089NIH HHS R01 OD020376NINDS NIH HHS R01 NS095355
6 · The paper itself

Abstract

Transgenic expression of bacterial nitroreductase (NTR) enzymes sensitizes eukaryotic cells to prodrugs such as metronidazole (MTZ), enabling selective cell-ablation paradigms that have expanded studies of cell function and regeneration in vertebrates. However, first-generation NTRs required confoundingly toxic prodrug treatments to achieve effective cell ablation, and some cell types have proven resistant. Here we used rational engineering and cross-species screening to develop an NTR variant, NTR 2.0, which exhibits ~100-fold improvement in MTZ-mediated cell-specific ablation efficacy, eliminating the need for near-toxic prodrug treatment regimens. NTR 2.0 therefore enables sustained cell-loss paradigms and ablation of previously resistant cell types. These properties permit enhanced interrogations of cell function, extended challenges to the regenerative capacities of discrete stem cell niches, and novel modeling of chronic degenerative diseases. Accordingly, we have created a series of bipartite transgenic reporter/effector resources to facilitate dissemination of NTR 2.0 to the research community.

Indexed as

AnimalsAnimals, Genetically ModifiedCHO CellsCricetulusGreen Fluorescent ProteinsHEK293 CellsHumansMetronidazoleNitroreductasesProdrugsProtein EngineeringRecombinant ProteinsRetinaVibrioZebrafishGreen Fluorescent ProteinsMetronidazoleNitroreductasesProdrugsRecombinant Proteins

Identifiers

PMID35132245
PMCPMC8851868
OpenAlexW4220893419

What OpenQuestion holds

Textmetadata
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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.