Evidence map›Paper›PMID 33179507›Full record

ArticleACS synthetic biology2020

Creating Red Light-Switchable Protein Dimerization Systems as Genetically Encoded Actuators with High Specificity.

Zhimin Huang, Zengpeng Li, Xiao Zhang, Shoukai Kang, Runze Dong, Li Sun, Xiaonan Fu, David Vaisar, Kurumi Watanabe, Liangcai Gu

Open access · greenAbstract read
In one paragraph

Article in ACS synthetic biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.5field-weighted citation impact, top 20% 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

23 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Optogenetic engineering for precision cancer immunotherapy.Trends in pharmacological sciences · 2025
    Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Engineering activatable promoters for scalable and multi-input CRISPRa/i circuits.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  16. Review
  17. Article
  18. Review
  19. Review
  20. Red-shifted optogenetics comes to the spotlight.Clinical and translational medicine · 2022
    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

10 authors at 1 institution in 2 countries.

Zhimin HuangDepartment of Biochemistry and Institute for Protein Design, University of Washington, Seattle, Washington 98195, United States.ORCID 0000-0001-9230-6039
Zengpeng LiDepartment of Biochemistry and Institute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
Xiao ZhangDepartment of Biochemistry and Institute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
Shoukai KangDepartment of Biochemistry and Institute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
Runze DongDepartment of Biochemistry and Institute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
Li SunDepartment of Biochemistry and Institute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
Xiaonan FuDepartment of Biochemistry and Institute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
David VaisarDepartment of Biochemistry and Institute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
Kurumi WatanabeDepartment of Biochemistry and Institute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
Liangcai GuDepartment of Biochemistry and Institute for Protein Design, University of Washington, Seattle, Washington 98195, United States.ORCID 0000-0002-8232-6025
University of Washington · US

Funding

De Novo Engineering of Small Molecule-Actuatable Biosensors for Cell TherapyR35GM128918 · NIGMS · UNIVERSITY OF WASHINGTON · PI GU, LIANGCAI · 2018 to 2022
$2.1M
NIGMS NIH HHS R35 GM128918
6 · The paper itself

Abstract

Protein dimerization systems controlled by red light with increased tissue penetration depth are a highly needed tool for clinical applications such as cell and gene therapies. However, mammalian applications of existing red light-induced dimerization systems are hampered by limitations of their two components: a photosensory protein (or photoreceptor) which often requires a mammalian exogenous chromophore and a naturally occurring photoreceptor binding protein typically having a complex structure and nonideal binding properties. Here, we introduce an efficient, generalizable method (COMBINES-LID) for creating highly specific, reversible light-induced heterodimerization systems independent of any existing binders to a photoreceptor. It involves a two-step binder screen (phage display and yeast two-hybrid) of a combinatorial nanobody library to obtain binders that selectively engage a light-activated form of a photoswitchable protein or domain not the dark form. Proof-of-principle was provided by engineering nanobody-based, red light-induced dimerization (nanoReD) systems comprising a truncated bacterial phytochrome sensory module using a mammalian endogenous chromophore, biliverdin, and light-form specific nanobodies. Selected nanoReD systems were biochemically characterized, exhibiting low dark activity and high induction specificity, and further demonstrated for the reversible control of protein translocation and activation of gene expression in mice. Overall, COMBINES-LID opens new opportunities for creating genetically encoded actuators for the optical manipulation of biological processes.

Indexed as

LightAnimalsCalorimetryDeinococcusDimerizationHEK293 CellsHumansInterferometryMaleMiceMice, Inbred BALB CPeptide LibraryPhytochromePlasmidsSingle-Chain AntibodiesTranscriptional ActivationPeptide LibraryPhytochromeSingle-Chain Antibodiesbacterial phytochromecombinatorial antibody librarylight-induced dimerizationnanobodyoptogeneticsphage display

Identifiers

PMID33179507
PMCPMC7749050
OpenAlexW3100622014

What OpenQuestion holds

Textmetadata
LicenceTDM
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.