Amplification editing enables efficient and precise duplication of DNA from short sequence to megabase and chromosomal scale.
Cell
; 187(15): 3936-3952.e19, 2024 Jul 25.
Article
em En
| MEDLINE
| ID: mdl-38936359
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Genoma Humano
/
Duplicação Gênica
/
Edição de Genes
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2024
Tipo de documento:
Article
País de publicação:
Estados Unidos