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

Cell

Departments of Urology and Laboratory Medicine, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, State Key Laboratory of Virology, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan 430071, China. Electronic address:

Published: July 2024

AI Article Synopsis

  • Duplication plays a crucial role in molecular evolution and various diseases; researchers have developed a tool called Amplification Editing (AE) for precise DNA duplication.
  • AE can duplicate substantial portions of human genomes, ranging from 20 bp to 100 Mb, with varying efficiencies depending on the size of the duplication.
  • This tool has the potential to create microduplications in disease-related areas within embryonic stem cells, paving the way for advancements in cellular and animal model research.

Article 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-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.

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http://dx.doi.org/10.1016/j.cell.2024.05.056DOI Listing

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