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dc.contributor.authorSuzuki, Keiichiro
dc.contributor.authorYamamoto, Mako
dc.contributor.authorHernandez-Benitez, Reyna
dc.contributor.authorLi, Zhe
dc.contributor.authorWei, Christopher
dc.contributor.authorSoligalla, Rupa Devi
dc.contributor.authorAizawa, Emi
dc.contributor.authorHatanaka, Fumiyuki
dc.contributor.authorKurita, Masakazu
dc.contributor.authorReddy, Pradeep
dc.contributor.authorOcampo, Alejandro
dc.contributor.authorHishida, Tomoaki
dc.contributor.authorSakurai, Masahiro
dc.contributor.authorNemeth, Amy N
dc.contributor.authorNuñez Delicado, Estrella
dc.contributor.authorCampistol, Josep M
dc.contributor.authorMagistretti, Pierre J.
dc.contributor.authorGuillen, Pedro
dc.contributor.authorRodriguez Esteban, Concepcion
dc.contributor.authorGong, Jianhui
dc.contributor.authorYuan, Yilin
dc.contributor.authorGu, Ying
dc.contributor.authorLiu, Guang-Hui
dc.contributor.authorLópez-Otín, Carlos
dc.contributor.authorWu, Jun
dc.contributor.authorZhang, Kun
dc.contributor.authorIzpisua Belmonte, Juan Carlos
dc.date.accessioned2019-08-26T05:22:58Z
dc.date.available2019-08-26T05:22:58Z
dc.date.issued2019-08-23
dc.identifier.citationSuzuki, K., Yamamoto, M., Hernandez-Benitez, R., Li, Z., Wei, C., Soligalla, R. D., … Izpisua Belmonte, J. C. (2019). Precise in vivo genome editing via single homology arm donor mediated intron-targeting gene integration for genetic disease correction. Cell Research. doi:10.1038/s41422-019-0213-0
dc.identifier.doi10.1038/s41422-019-0213-0
dc.identifier.urihttp://hdl.handle.net/10754/656597
dc.description.abstractIn 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.
dc.description.sponsorshipWe are grateful to M. Schwarz and P. Schwarz for administrative help; D. O’Keefe and S. Tsuji for help with manuscript preparation; M. Kay and Z.Y. Chen for sharing experimental materials; J. Naughton and J. Marlett for AAV production; K. Peterson and Y. Gu for helping the measurement of heart rate; U. Manor and K. Diffenderfer for imaging; K. McIntyre for mouse histology processing and J. Li for helping the molecular work; K. Sumiyama for data analysis. M.Y. was partially supported by 2016 Salk Women & Science Special Award. K.S. was supported by JSPS KAKENHI (15K21762 and 18H04036), Takeda Science Foundation, The Uehara Memorial Foundation, National Institutes of Natural Sciences (BS291007), The Sumitomo Foundation (170220), The Naito Foundation, The Kurata Grants (1350), Mochida Memorial Foundation, and The Inamori Foundation. This research was supported by Guangdong Provincial Key Laboratory of Genome Read and Write (No. 2017B030301011), Guangdong Provincial Academician Workstation of BGI Synthetic Genomics (No. 2017B090904014) and Shenzhen Peacock Plan (No. KQTD20150330171505310). J.C.I.B. was supported by The Leona M. and Harry B. Helmsley Charitable Trust (2012-PG-MED002), the G. Harold and Leila Y. Mathers Charitable Foundation, NIH (R01HL123755 and 5 DP1 DK113616), The Progeria Research Foundation, The Glenn Foundation, KAUST, The Moxie Foundation, Fundación Dr. Pedro Guillen, AFE and Universidad Católica San Antonio de Murcia (UCAM).
dc.publisherSpringer Nature
dc.relation.urlhttp://www.nature.com/articles/s41422-019-0213-0
dc.rightsArchived with thanks to Cell research
dc.titlePrecise in vivo genome editing via single homology arm donor mediated intron-targeting gene integration for genetic disease correction.
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
dc.identifier.journalCell research
dc.rights.embargodate2020-02-25
dc.eprint.versionPost-print
dc.contributor.institutionGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.
dc.contributor.institutionInstitute for Advanced Co-Creation Studies, Osaka University, Osaka, 560-8531, Japan
dc.contributor.institutionGraduate School of Engineering Science, Osaka University, Osaka, 560-8531, Japan
dc.contributor.institutionBioengineering, University of California, San Diego, 9500 Gilman Drive, MC0412, La Jolla, CA, 92093-0412, USA.
dc.contributor.institutionUniversidad Catolica, San Antonio de Murcia, Campus de los Jeronimos, 135, Guadalupe, 30107, Spain.
dc.contributor.institutionHospital Clinic of Barcelona, Carrer Villarroel, 170, 08036, Barcelona, Spain.
dc.contributor.institutionFundacion Dr. Pedro Guillen, Clinica CEMTRO, Avenida Ventisquero de la Condesa, 4228035, Madrid, Spain.
dc.contributor.institutionBGI-Shenzhen, Shenzhen, 518083, China.
dc.contributor.institutionGuangdong Provincial Key Laboratory of Genome Read and Write, Shenzhen, 518120, China
dc.contributor.institutionGuangdong Provincial Academician Workstation of BGI Synthetic Genomics, BGI-Shenzhen, Guangdong, China
dc.contributor.institutionShenzhen Engineering Laboratory for Innovative Molecular Diagnostics, Shenzhen, 518120, China
dc.contributor.institutionNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
dc.contributor.institutionNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
dc.contributor.institutionDepartamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología (IUOPA), Universidad de Oviedo, Oviedo, Spain.
dc.contributor.institutionDepartment of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
dc.contributor.institutionHamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
kaust.personMagistretti, Pierre J.


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