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

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

  • Cell. 2024 Jul 25;187(15):3936-3952.e19. doi: 10.1016/j.cell.2024.05.056.
Ruiwen Zhang 1,  Zhou He 2,  Yajing Shi 2,  Xiangkun Sun 2,  Xinyu Chen 2,  Guoquan Wang 2,  Yizhou Zhang 2,  Pan Gao 2,  Ying Wu 2,  Shuhan Lu 2,  Junyi Duan 2,  Shangwu Sun 3,  Na Yang 4,  Wei Fan 5,  Kaitao Zhao 6,  Bei Yang 3,  Yuchen Xia 6,  Yan Zhang 7,  Ying Zhang 1,  Hao Yin 8
Affiliations

Affiliations

  • 1 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; Department of Rheumatology and Immunology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
  • 2 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.
  • 3 Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
  • 4 Center for Gene Diagnosis and Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
  • 5 Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
  • 6 State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, Institute of Medical Virology, TaiKang Center for Life and Medical Sciences, TaiKang Medical School, Wuhan University, Wuhan 430071, China.
  • 7 Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, China.
  • 8 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: haoyin@whu.edu.cn.
PMID: 38936359 DOI: 10.1016/j.cell.2024.05.056
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.

Keywords

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

Figures
Products