A mitochondrial disease model is generated and corrected using engineered base editors in rat zygotes

IF 33.1 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Nature biotechnology Pub Date : 2025-06-03 DOI:10.1038/s41587-025-02684-y

Liang Chen, Changming Luan, Mengjia Hong, Meng Yuan, Hao Huang, Debo Gao, Xinyuan Guo, Zhengxin Chen, Yongmei Li, Lei Yang, Zongyi Yi, Wensheng Wei, Mingyao Liu, Liangcai Gao, Honghui Han, Dali Li

引用次数: 0

Abstract

Efficient generation and correction of mutations in mitochondrial DNA (mtDNA) is challenging. Here, through embryonic injection of an mtDNA adenine base editor (eTd-mtABE), Leigh syndrome rat models were generated efficiently (up to 74%) in the F₀ generation, exhibiting severe defects. To correct this mutation, a precise mtDNA C-to-T base editor was engineered and injected into mutated embryos. It achieved restoration of wild-type alleles to an average of 53%, leading to amelioration of disease symptoms.

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在大鼠受精卵中使用工程碱基编辑器生成和纠正线粒体疾病模型

有效地产生和纠正线粒体DNA （mtDNA）突变是具有挑战性的。在这里，通过胚胎注射mtDNA腺嘌呤碱基编辑器（eTd-mtABE），在F0代高效生成Leigh综合征大鼠模型（高达74%），显示出严重的缺陷。为了纠正这种突变，一个精确的mtDNA C-to-T碱基编辑器被设计并注入突变的胚胎中。它使野生型等位基因的平均恢复率达到53%，从而改善了疾病症状。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature biotechnology 工程技术-生物工程与应用微生物

CiteScore

63.00

自引率

1.70%

发文量

382

审稿时长

3 months

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