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Amplification editing enables efficient and precise duplication of DNA from short sequence to megabase and chromosomal scale

Cell. 2024-07; 
Ruiwen Zhang , Zhou He , Yajing Shi , Xiangkun Sun , Xinyu Chen , Guoquan Wang , Yizhou Zhang , Pan Gao , Ying Wu , Shuhan Lu , Junyi Duan , Shangwu Sun , Na Yang , Wei Fan , Kaitao Zhao , Bei Yang , Yuchen Xia , Yan Zhang , Ying Zhang , Hao Yin
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Abstract

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-re... More

Keywords

amplification editing; chromosomal microduplication; gene duplication; genome editing; precision editing at chromosomal scale; precision editing of structural variation; tandem repeats.