Evidence map›Paper›PMID 39288267›Full record

ArticleThe Journal of clinical investigation2024

CRISPR/Cas13d targeting suppresses repeat-associated non-AUG translation of C9orf72 hexanucleotide repeat RNA.

Honghe Liu, Xiao-Feng Zhao, Yu-Ning Lu, Lindsey R Hayes, Jiou Wang

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2024. 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 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Honghe LiuDepartment of Biochemistry and Molecular Biology, Bloomberg School of Public Health, and.
Xiao-Feng ZhaoDepartment of Biochemistry and Molecular Biology, Bloomberg School of Public Health, and.
Yu-Ning LuDepartment of Biochemistry and Molecular Biology, Bloomberg School of Public Health, and.
Lindsey R HayesBrain Science Institute and Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jiou WangDepartment of Biochemistry and Molecular Biology, Bloomberg School of Public Health, and.

Funding

Neurodegeneration and Proteotoxicity Dissected in C. elegans and MammalsR01NS074324 · NINDS · JOHNS HOPKINS UNIVERSITY · PI WANG, JIOU · 2011 to 2025
$6.2M
Investigating the role of C9orf72 in autophagic and metabolic dysregulation in ALS/FTDR01NS089616 · NINDS · JOHNS HOPKINS UNIVERSITY · PI Jiou Wang · 2015 to 2026
$6.0M
Mechanisms of RNA and Protein Dysregulations in ALS/FTD Associated with FUS and Ubiquilin 2R01NS110098 · NINDS · JOHNS HOPKINS UNIVERSITY · PI Jiou Wang · 2019 to 2026
$5.0M
Molecular Basis of Pathogenic Cascades in ALS/FTD Initiated from C9orf72 Hexanucleotide Repeat ExpansionR01NS128494 · NINDS · JOHNS HOPKINS UNIVERSITY · PI Jiou Wang · 2022 to 2026
$3.1M
RNA-based regulation of TDP-43 nuclear export in ALS/FTDR01NS123538 · NINDS · JOHNS HOPKINS UNIVERSITY · PI HOKE, AHMET · 2021 to 2025
$2.4M
NINDS NIH HHS R01 NS074324NINDS NIH HHS R01 NS089616NINDS NIH HHS R01 NS110098NINDS NIH HHS R01 NS123538NINDS NIH HHS R01 NS128494
6 · The paper itself

Abstract

A hexanucleotide GGGGCC repeat expansion in the non-coding region of the C9orf72 gene is the most common genetic mutation identified in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The resulting repeat RNA and dipeptide repeat proteins from non-conventional repeat translation have been recognized as important markers associated with the diseases. CRISPR/Cas13d, a powerful RNA-targeting tool, has faced challenges in effectively targeting RNA with stable secondary structures. Here we report that CRISPR/Cas13d can be optimized to specifically target GGGGCC repeat RNA. Our results demonstrate that the CRISPR/Cas13d system can be harnessed to significantly diminish the translation of poly-dipeptides originating from the GGGGCC repeat RNA. This efficacy has been validated in various cell types, including induced pluripotent stem cells and differentiated motor neurons originating from C9orf72-ALS patients, as well as in C9orf72 repeat transgenic mice. These findings demonstrate the application of CRISPR/Cas13d in targeting RNA with intricate higher-order structures and suggest a potential therapeutic approach for ALS and FTD.

Indexed as

Amyotrophic Lateral SclerosisC9orf72 ProteinCRISPR-Cas SystemsDNA Repeat ExpansionFrontotemporal DementiaMice, TransgenicAnimalsHumansInduced Pluripotent Stem CellsMiceMotor NeuronsProtein BiosynthesisRNAC9orf72 ProteinC9orf72 protein, humanC9orf72 protein, mouseRNAGene therapyGeneticsMolecular biologyNeurodegenerationNeuroscience

Identifiers

PMID39288267
PMCPMC11527445

What Socratic 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 Socratic graph.