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

Publicado en: Nature Communications

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 prematureaging 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.


Suzuki K, Yamamoto M, Hernandez-Benitez R, Li Z, Wei C, Devi Soligalla R, 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, Gong J, Yuan Y, Gu Y, Liu G-H, López-Otín C, Wu J, Zhang K, Izpisua Belmonte JC. Precise in vivo genome editing via one-homology armed donor mediated intron-targeting gene integration. Cell Res. 2019 Oct;29(10):804-819. doi: 10.1038/s41422-019-0213-0. Epub 2019 Aug 23.


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