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

Keiichiro Suzuki, Mako Yamamoto, Reyna Hernandez-Benitez, Zhe Li, Christopher Wei, Rupa Devi Soligalla, Emi Aizawa, Fumiyuki Hatanaka, Masakazu Kurita, Pradeep Reddy, Alejandro Ocampo, Tomoaki Hishida, Masahiro Sakurai, Amy N Nemeth, Estrella Nuñez Delicado, Josep M Campistol, Pierre J. Magistretti, Pedro Guillen, Concepcion Rodriguez Esteban, Jianhui GongYilin Yuan, Ying Gu, Guang-Hui Liu, Carlos López-Otín, Jun Wu, Kun Zhang, Juan Carlos Izpisua Belmonte

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.
Original languageEnglish (US)
Pages (from-to)804-819
Number of pages16
JournalCell research
Volume29
Issue number10
DOIs
StatePublished - Aug 23 2019

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