Evidence map›Paper›PMID 40164764›Full record

ArticleNature biotechnology2026

Circular RNA aptamers targeting neuroinflammation ameliorate Alzheimer disease phenotypes in mouse models.

Xin Feng, Bo-Wen Jiang, Si-Nan Zhai, Chu-Xiao Liu, Hao Wu, Bang-Qi Zhu, Meng-Yuan Wei, Jia Wei, Li Yang, Ling-Ling Chen

Erratum issuedAbstract read
PubMed Publisher
In one paragraph

Article in Nature biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. Article
  2. Distinct cell type-specific mechanisms underlie cognitive dysfunction during persistent integrated stress response activation.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Circular RNAEnvironment & health (Washington, D.C.) · 2026
    Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
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  14. Article
  15. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Xin Feng *Key Laboratory of RNA Innovation, Science and Engineering, New Cornerstone Science Laboratory, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Bo-Wen Jiang *Key Laboratory of RNA Innovation, Science and Engineering, New Cornerstone Science Laboratory, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Si-Nan ZhaiCenter for Molecular Medicine, Children's Hospital of Fudan University and Shanghai Key Laboratory of Medical Epigenetics, International Laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Chu-Xiao LiuKey Laboratory of RNA Innovation, Science and Engineering, New Cornerstone Science Laboratory, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0000-0002-6725-8327
Hao WuKey Laboratory of RNA Innovation, Science and Engineering, New Cornerstone Science Laboratory, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Bang-Qi ZhuKey Laboratory of RNA Innovation, Science and Engineering, New Cornerstone Science Laboratory, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Meng-Yuan WeiKey Laboratory of RNA Innovation, Science and Engineering, New Cornerstone Science Laboratory, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Jia WeiCenter for Molecular Medicine, Children's Hospital of Fudan University and Shanghai Key Laboratory of Medical Epigenetics, International Laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Li YangCenter for Molecular Medicine, Children's Hospital of Fudan University and Shanghai Key Laboratory of Medical Epigenetics, International Laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0001-8833-7473
Ling-Ling ChenKey Laboratory of RNA Innovation, Science and Engineering, New Cornerstone Science Laboratory, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. linglingchen@sibcb.ac.cn.ORCID http://orcid.org/0000-0001-9501-0305

Funding

Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission) grant no. 23DX1900100
6 · The paper itself

Abstract

Alzheimer disease (AD) therapy may benefit from optimized approaches to inhibit neuroinflammation. Small-molecule inhibitors of the proinflammatory molecule double-stranded RNA (dsRNA)-activated protein kinase R (PKR) have efficacy in AD models but their utility is compromised by adverse side effects. Here, we target PKR in two mouse models of AD using circular RNAs containing short double-stranded regions (ds-cRNAs), which are structurally similar to what we used previously to target PKR in psoriasis models. We show that the intrahippocampal injection of ds-cRNAs to neurons and microglia by adeno-associated virus (AAV) effectively dampens excessive PKR activity with minimal toxicity, accompanied by reduced neuroinflammation and amyloid-β plaques. We also deliver ds-cRNAs to the whole brain through intravenous injection of AAV-PHP.eB, which crosses the blood-brain barrier, resulting in neuroprotection and enhanced capability of spatial learning and memory in AD mouse models. The delivery of ds-cRNAs at different progressive stages of AD alleviates disease phenotypes, with therapeutic effects sustained for at least 6 months after a single administration.

Indexed as

Alzheimer DiseaseAptamers, NucleotideNeuroinflammatory DiseasesRNA, CircularAnimalsDependovirusDisease Models, AnimaleIF-2 KinaseHumansMiceMice, TransgenicMicrogliaNeuronsPhenotypeAptamers, NucleotideeIF-2 KinaseRNA, Circular

Identifiers

PMID40164764

What OpenQuestion holds

Textmetadata
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.