TY - JOUR
T1 - Precise in vivo genome editing via single homology arm donor mediated intron-targeting gene integration for genetic disease correction
AU - Suzuki, Keiichiro
AU - Yamamoto, Mako
AU - Hernandez-Benitez, Reyna
AU - Li, Zhe
AU - Wei, Christopher
AU - Soligalla, Rupa Devi
AU - Aizawa, Emi
AU - Hatanaka, Fumiyuki
AU - Kurita, Masakazu
AU - Reddy, Pradeep
AU - Ocampo, Alejandro
AU - Hishida, Tomoaki
AU - Sakurai, Masahiro
AU - Nemeth, Amy N.
AU - Nuñez Delicado, Estrella
AU - Campistol, Josep M.
AU - Magistretti, Pierre
AU - Guillen, Pedro
AU - Rodriguez Esteban, Concepcion
AU - Gong, Jianhui
AU - Yuan, Yilin
AU - Gu, Ying
AU - Liu, Guang Hui
AU - López-Otín, Carlos
AU - Wu, Jun
AU - Zhang, Kun
AU - Izpisua Belmonte, Juan Carlos
N1 - Publisher Copyright:
© 2019, IBCB, SIBS, CAS.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85071504608&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071504608&partnerID=8YFLogxK
U2 - 10.1038/s41422-019-0213-0
DO - 10.1038/s41422-019-0213-0
M3 - Article
C2 - 31444470
AN - SCOPUS:85071504608
SN - 1001-0602
VL - 29
SP - 804
EP - 819
JO - Cell Research
JF - Cell Research
IS - 10
ER -