Duplication is a foundation of molecular evolution and a driver of genomic and complex diseases. Here, we develop a genome editing tool named Amplification Editing (AE) that enables programmable DNA duplication with precision at chromosomal scale. AE can duplicate human genomes ranging from 20 bp to 100 Mb, a size comparable to human chromosomes. AE exhibits activity across various cell types, encompassing diploid, haploid, and primary cells. AE exhibited up to 73.0% efficiency for 1 Mb and 3.4% for 100 Mb duplications, respectively. Whole-genome sequencing and deep sequencing of the junctions of edited sequences confirm the precision of duplication. AE can create chromosomal microduplications within disease-relevant regions in embryonic stem cells, indicating its potential for generating cellular and animal models. AE is a precise and efficient tool for chromosomal engineering and DNA duplication, broadening the landscape of precision genome editing from an individual genetic locus to the chromosomal scale.

中文翻译：

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扩增编辑可实现从短序列到兆碱基和染色体规模的 DNA 高效、精确复制


复制是分子进化的基础，也是基因组和复杂疾病的驱动因素。在这里，我们开发了一种名为扩增编辑（AE）的基因组编辑工具，可以在染色体规模上实现精确的可编程 DNA 复制。 AE 可以复制 20 bp 至 100 Mb 的人类基因组，其大小与人类染色体相当。 AE 在多种细胞类型中表现出活性，包括二倍体、单倍体和原代细胞。 AE 对于 1 Mb 重复表现出高达 73.0% 的效率，对于 100 Mb 重复表现出高达 3.4% 的效率。全基因组测序和编辑序列连接处的深度测序证实了复制的精度。 AE 可以在胚胎干细胞的疾病相关区域内产生染色体微复制，这表明它具有生成细胞和动物模型的潜力。 AE 是一种用于染色体工程和 DNA 复制的精确而高效的工具，将精确基因组编辑的范围从单个基因位点扩大到染色体规模。