Evidence map›Paper›PMID 41526374›Full record

ArticleNature communications2026

Precise excision of expanded GGC repeats in NOTCH2NLC via CRISPR/Cas9 for treating neuronal intranuclear inclusion disease.

Nina Xie, Yongcheng Pan, Huichun Tong, Yingqi Lin, Ying Jiang, Zhiqin Wang, Juan Wan, Wendiao Zhang, Xinhui Wang, Xiaobo Sun and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. 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. 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

22 authors.

Nina Xie *Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yongcheng Pan *Key Laboratory of Hunan Province in Neurodegenerative Disorders & Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.ORCID http://orcid.org/0000-0001-5317-3675
Huichun TongGuangdong Provincial Key Laboratory of Non-human Primate Research, Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China.
Yingqi LinGuangdong Provincial Key Laboratory of Non-human Primate Research, Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China.
Ying JiangCentre for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
Zhiqin WangDepartment of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Juan WanDepartment of Neurology, Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Wendiao ZhangDepartment of Neurology, Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.ORCID http://orcid.org/0000-0002-3510-8383
Xinhui WangKey Laboratory of Hunan Province in Neurodegenerative Disorders & Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Xiaobo SunSchool of Statistics and Mathematics, Zhongnan University of Economics And Law, Wuhan, Hubei, China.
Sen YanGuangdong Provincial Key Laboratory of Non-human Primate Research, Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China.ORCID http://orcid.org/0000-0003-4889-1570
Peng YinGuangdong Provincial Key Laboratory of Non-human Primate Research, Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China.ORCID http://orcid.org/0000-0002-4811-6956
Qiying SunDepartment of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Chengzhi QiSchool of Statistics and Mathematics, Zhongnan University of Economics And Law, Wuhan, Hubei, China.
Yun TianDepartment of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Lu ShenKey Laboratory of Hunan Province in Neurodegenerative Disorders & Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.ORCID http://orcid.org/0000-0002-3393-8578
Hong JiangKey Laboratory of Hunan Province in Neurodegenerative Disorders & Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Desheng LiangCentre for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.ORCID http://orcid.org/0000-0002-9451-8585
Beisha TangKey Laboratory of Hunan Province in Neurodegenerative Disorders & Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.ORCID http://orcid.org/0000-0003-2120-1576
Shihua LiGuangdong Provincial Key Laboratory of Non-human Primate Research, Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China. lishihualis@jnu.edu.cn.ORCID http://orcid.org/0000-0003-1775-6536
Xiao-Jiang LiGuangdong Provincial Key Laboratory of Non-human Primate Research, Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China. xjli33@jnu.edu.cn.ORCID http://orcid.org/0000-0002-9370-8838
Qiong LiuKey Laboratory of Hunan Province in Neurodegenerative Disorders & Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China. lqiong66@csu.edu.cn.ORCID http://orcid.org/0000-0002-2591-8550

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32071037
6 · The paper itself

Abstract

Neuronal intranuclear inclusion disease (NIID) is an adult-onset neurodegenerative disease caused by expanded GGC repeats in the 5' untranslated region of the human-specific NOTCH2NLC gene. The high sequence similarity between NOTCH2NLC and its paralogs poses a significant challenge for precise gene editing. Here, we develop a CRISPR/spCas9-based gene-editing strategy that precisely excises the expanded GGC repeats in NOTCH2NLC without detectable off-target effects on the highly homologous NOTCH2/NOTCH2NL family genes (<2% sequence divergence at this locus). The efficacy, specificity and safety of this approach are rigorously validated across multiple experimental models, including human cell lines, NIID iPSCs, and our previously established transgenic NIID mouse model. Our results demonstrate that precise excision of the expanded GGC repeats effectively alleviates NIID-related neuropathological, molecular and behavioral abnormalities. This study establishes the proof of concept for genome editing as a therapeutic strategy for NIID and other related repeat expansion disorders.

Indexed as

CRISPR-Cas SystemsGene EditingIntranuclear Inclusion BodiesNeurodegenerative DiseasesReceptor, Notch2Trinucleotide Repeat ExpansionAnimalsDisease Models, AnimalHumansInduced Pluripotent Stem CellsIntercellular Signaling Peptides and ProteinsMiceMice, TransgenicNerve Tissue ProteinsNeuronsIntercellular Signaling Peptides and ProteinsNerve Tissue ProteinsNOTCH2NLC protein, humanReceptor, Notch2

Identifiers

PMID41526374
PMCPMC12909857

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.