Evidence map›Paper›PMID 36127368›Full record

ArticleNature communications2022

Systematic profiling of conditional degron tag technologies for target validation studies.

Daniel P Bondeson, Zachary Mullin-Bernstein, Sydney Oliver, Thomas A Skipper, Thomas C Atack, Nolan Bick, Meilani Ching, Andrew A Guirguis, Jason Kwon, Carly Langan and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing 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

27 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Elucidating Gene Functions in Congenital Heart Disease.Current treatment options in cardiovascular medicine · 2026
    Review
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  7. Article
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  11. Article
  12. Article
  13. Gene regulation technologies for gene and cell therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Daniel P BondesonThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Zachary Mullin-BernsteinThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Sydney OliverThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Thomas A SkipperThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Thomas C AtackThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0001-5953-2261
Nolan BickThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Meilani ChingThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Andrew A GuirguisThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0003-3134-0596
Jason KwonThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Carly LanganThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Dylan MillsonThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Brenton R PaolellaThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0003-3394-828X
Kevin TranPeter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Sarah J WieThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Francisca VazquezThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Zuzana TothovaThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Todd R GolubThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0003-0113-2403
William R Sellers *The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-3539-9803
Alessandra Ianari *The Broad Institute of MIT and Harvard, Cambridge, MA, USA. aleianari12@gmail.com.

Funding

Making cancer precision medicine real: bottlenecks and opportunitiesR35CA242457 · NCI · BROAD INSTITUTE, INC. · PI GOLUB, TODD R. · 2019 to 2025
$6.9M
The function of the PRMT5 methylosome in MTAP deleted cancersR01CA233626 · NCI · BROAD INSTITUTE, INC. · PI Andrew James Aguirre, WILLIAM R SELLERS · 2019 to 2026
$2.9M
Investigating degradation as a therapeutic strategy against the Pseudo-kinase KSRK00CA212229 · NCI · BROAD INSTITUTE, INC. · PI BONDESON, DANIEL · 2018 to 2021
$363k
Investigating degradation as a therapeutic strategy against the Pseudo-kinase KSRF99CA212229 · NCI · YALE UNIVERSITY · PI BONDESON, DANIEL · 2016 to 2017
$89k
NCI NIH HHS F99 CA212229NCI NIH HHS K00 CA212229NCI NIH HHS R01 CA233626NCI NIH HHS R35 CA242457
6 · The paper itself

Abstract

Conditional degron tags (CDTs) are a powerful tool for target validation that combines the kinetics and reversible action of pharmacological agents with the generalizability of genetic manipulation. However, successful design of a CDT fusion protein often requires a prolonged, ad hoc cycle of construct design, failure, and re-design. To address this limitation, we report here a system to rapidly compare the activity of five unique CDTs: AID/AID2, IKZF3d, dTAG, HaloTag, and SMASh. We demonstrate the utility of this system against 16 unique protein targets. We find that expression and degradation are highly dependent on the specific CDT, the construct design, and the target. None of the CDTs leads to efficient expression and/or degradation across all targets; however, our systematic approach enables the identification of at least one optimal CDT fusion for each target. To enable the adoption of CDT strategies more broadly, we have made these reagents, and a detailed protocol, available as a community resource.

Indexed as

ProteolysisKinetics

Identifiers

PMID36127368
PMCPMC9489723

What OpenQuestion holds

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LicenceCC BY
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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.