Journal
EBIOMEDICINE
Volume 20, Issue -, Pages 19-26Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ebiom.2017.05.015
Keywords
MMEJ; CRISPR/Cas9; In vivo targeted integration; Fah(-/-) mice; Gene therapy
Funding
- CAS Strategic Priority Research Program [XDB02050007, XDA01010409]
- MoST863 Program [2015AA020307]
- NSFC [31522037, 31500825]
- China Youth Thousand Talents Program
- Break through project of Chinese Academy of Sciences
- Ministry of Science and Technology of China (MOST) [2016YFA0100500]
- National Natural Science Foundation of China (NSFC) [31571509, 31522038]
- Shanghai Sailing Plan for the Young Scientific Talents [14YF1406900]
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Precisely targeted genome editing is highly desired for clinical applications. However, the widely used homology-directed repair (HDR)-based genome editing strategies remain inefficient for certain in vivo applications. We here demonstrate a microhomology-mediated end-joining (MMEJ)-based strategy for precisely targeted gene integration in transfected neurons and hepatocytes in vivo with efficiencies up to 20%, much higher (up to 10 fold) than HDR-based strategy in adult mouse tissues. As a proof of concept of its therapeutic potential, we demonstrate the efficacy of MMEJ-based strategy in correction of Fah mutation and rescue of Fah(-/-) liver failure mice, offering an efficient approach for precisely targeted gene therapies. (C) 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.
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