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.

中文翻译：

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使用大鼠受精卵中的工程碱基编辑器生成和校正线粒体疾病模型

线粒体 DNA （mtDNA） 突变的高效生成和校正具有挑战性。在这里，通过胚胎注射 mtDNA 腺嘌呤碱基编辑器 （eTd-mtABE），在 F₀ 代中有效生成 Leigh 综合征大鼠模型 （高达 74%），表现出严重的缺陷。为了纠正这种突变，设计了一个精确的 mtDNA C-to-T 碱基编辑器并将其注射到突变的胚胎中。它使野生型等位基因恢复到平均 53%，从而改善了疾病症状。