Evidence map›Paper›PMID 40271540›Full record

ArticleFrontiers in cellular neuroscience2025

A humanized Gs-coupled DREADD for circuit and behavior modulation.

Qi Zhang, Ruiqi Wang, Liang Zhang, Mengqi Li, Jianbang Lin, Xiaoyang Lu, Yixuan Tian, Yunping Lin, Taian Liu, Yefei Chen and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in cellular neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Overview of the DREADDs chemogenetics and the patent landscape of their actuators.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
    Review
  2. 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

16 authors.

Qi Zhang *Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, Harbin, China.
Ruiqi Wang *Research Center for Primate Neuromodulation and Neuroimaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Liang Zhang *Department of Anesthesiology, The Third People's Hospital of Shenzhen, Shenzhen, China.
Mengqi LiResearch Center for Primate Neuromodulation and Neuroimaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Jianbang LinResearch Center for Primate Neuromodulation and Neuroimaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Xiaoyang LuResearch Center for Primate Neuromodulation and Neuroimaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Yixuan TianResearch Center for Primate Neuromodulation and Neuroimaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Yunping LinResearch Center for Primate Neuromodulation and Neuroimaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Taian LiuResearch Center for Primate Neuromodulation and Neuroimaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Yefei ChenResearch Center for Primate Neuromodulation and Neuroimaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Yuantao LiShenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, China.
Jun CaoShenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, China.
Qiang WuDepartment of Anesthesiology, The Third People's Hospital of Shenzhen, Shenzhen, China.
Jinhui WangDepartment of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, Harbin, China.
Zhonghua LuResearch Center for Primate Neuromodulation and Neuroimaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Zexuan HongShenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Designer receptors exclusively activated by designer drugs (DREADDs) play important roles in neuroscience research and show great promise for future clinical interventions in neurological diseases. The Gs-coupled DREADD, rM3Ds, modulates excitability in neuron subsets that are sensitive to downstream effectors of Gs protein. However, given the non-human nature of the rM3Ds backbone, risks about potential immunogenicity and tolerability exist when considering clinical translation. Here, we report the development of a whole sequence-humanized Gs-coupled DREADD, hM3Ds. We found that hM3Ds has a comparable DREADD ligand response profile to rM3Ds. We then selectively expressed hM3Ds in D1 medium spiny neurons (D1-MSNs) and found that hM3Ds was able to activate the D1-MSNs-mediated basal ganglia direct pathway and alleviate Parkinsonian phenotypes in a Parkinson's disease mouse model. In conclusion, this engineered humanized Gs-coupled DREADD is suitable as an effective, and likely safer, DREADD tool for both research and future clinical applications.

Indexed as

D1-MSNsDREADDGs-signalingmodulationneuronal activationtransgene modification

Identifiers

PMID40271540
PMCPMC12015759

What OpenQuestion holds

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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.