Evidence map›Paper›PMID 34706494›Full record

ArticleHaematologica2022

Correction of RNA splicing defect in β

Dan Lu, Xiuli Gong, Yudan Fang, Xinbing Guo, Yanwen Chen, Fan Yang, Guijun Zhao, Qingwen Ma, Yitao Zeng, Fanyi Zeng

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Haematologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

14 citing papers in PubMed, 18 citations in OpenAlex.

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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 2 institutions in 1 country.

Dan LuShanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040.
Xiuli GongShanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040.
Yudan FangShanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040.
Xinbing GuoShanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040.
Yanwen ChenShanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040.
Fan YangShanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040.
Guijun ZhaoShanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040.
Qingwen MaShanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040.
Yitao ZengShanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040.
Fanyi ZengShanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, China; Department of Histo-Embryology, Genetics and Developmental Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Key Laboratory of Embryo Molecular Biology, Ministry of Health and Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai 200040. fzeng@vip.163.com.
Shanghai Jiao Tong University · CNShanghai Children's Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

β654-thalassemia is a prominent Chinese subtype of b-thalassemia, representing 17% of all cases of β-thalassemia in China. The molecular mechanism underlying this subtype involves the IVS-2-654 C→T mutation leading to aberrant β-globin RNA splicing. This results in an additional 73-nucleotide exon between exons 2 and 3 and leads to a severe thalassemia syndrome. Herein, we explored a CRISPR/Cas9 genome editing approach to eliminate the additional 73- nucleotide by targeting both the IVS-2-654 C→T and a cryptic acceptor splice site at IVS-2-579 in order to correct aberrant b-globin RNA splicing and ameliorate the clinical β-thalassemia syndrome in β654 mice. Gene-edited mice were generated by microinjection of sgRNA and Cas9 mRNA into one-cell embryos of β654 or control mice: 83.3% of live-born mice were gene-edited, 70% of which produced correctly spliced RNA. No off-target events were observed. The clinical symptoms, including hematologic parameters and tissue pathology of all of the edited β654 founders and their offspring were significantly improved compared to those of the non-edited β654 mice, consistent with the restoration of wild-type b-globin RNA expression. Notably, the survival rate of gene-edited heterozygous β654 mice increased significantly, and liveborn homozygous β654 mice were observed. Our study demonstrated a new and effective gene-editing approach that may provide groundwork for the exploration of β654-thalassemia therapy in the future.

Identifiers

PMID34706494
PMCPMC9152980
OpenAlexW3209892352

What OpenQuestion holds

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LicenceCC BY-NC
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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.