Precise in vivo genome editing via single homology arm donor mediated intron-targeting gene integration for genetic disease correction.

Abstract:

:In vivo genome editing represents a powerful strategy for both understanding basic biology and treating inherited diseases. However, it remains a challenge to develop universal and efficient in vivo genome-editing tools for tissues that comprise diverse cell types in either a dividing or non-dividing state. Here, we describe a versatile in vivo gene knock-in methodology that enables the targeting of a broad range of mutations and cell types through the insertion of a minigene at an intron of the target gene locus using an intracellularly linearized single homology arm donor. As a proof-of-concept, we focused on a mouse model of premature-aging caused by a dominant point mutation, which is difficult to repair using existing in vivo genome-editing tools. Systemic treatment using our new method ameliorated aging-associated phenotypes and extended animal lifespan, thus highlighting the potential of this methodology for a broad range of in vivo genome-editing applications.

journal_name

Cell Res

journal_title

Cell research

authors

Suzuki K,Yamamoto M,Hernandez-Benitez R,Li Z,Wei C,Soligalla RD,Aizawa E,Hatanaka F,Kurita M,Reddy P,Ocampo A,Hishida T,Sakurai M,Nemeth AN,Nuñez Delicado E,Campistol JM,Magistretti P,Guillen P,Rodriguez Esteban C,G

doi

10.1038/s41422-019-0213-0

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

804-819

issue

10

eissn

1001-0602

issn

1748-7838

pii

10.1038/s41422-019-0213-0

journal_volume

29

pub_type

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