In vivo genome editing partially restores alpha1-antitrypsin in a murine model of AAT deficiency
Author:  Date:2018-03-29  Clicks:

Hum Gene Ther.2018 Mar 29. doi: 10.1089/hum.2017.225. [Epub ahead of print]

Invivogenomeeditingpartiallyrestoresalpha1-antitrypsinin amurinemodelofAATdeficiency.

Song CQ1,Wang D2,Jiang T3,O'Connor K4,Tang Q5,Cai L6,Li X7,Weng Z8,Yin H9,Gao G10,11,Mueller C12,Flotte TR13,Xue W14.

Author information


CRISPRgenomeeditingholds promise in the treatment of genetic diseases that currently lack effective long-term therapies. Patients with Alpha-1 Antitrypsin (AAT)deficiencydevelop progressive lung disease due to the loss ofAAT's antiprotease function and liver disease due to a toxic gain of function of the common mutant allele. However, it remains unknown whether CRISPR-mediatedAATcorrection in the liver, whereAATis primarily expressed, can correct either or both defects. Here we show that AAV delivery of CRISPR can effectively correct Z-AATmutation in the liver of a transgenic mousemodel. Specifically, we co-injected two AAV: one expressing Cas9 and another encoding anAATguide RNA and homology-dependent repair template. In both neonate and adult mice, this treatmentpartiallyrestored M-AATin the serum. Furthermore, deep sequencing confirmed both indel mutations and precise gene correction in the liver, permitting careful analysis of geneeditingevents invivo. This study demonstrates a proof-of-concept for the application of CRISPR-Cas9 technology to correctAATmutations invivoand validates continued exploration of this approach for the treatment of patients withAATdeficiency.

Tel: 0086-27-68750205 Fax: 0086-27-68759675  Email:

Contact address: Donghu Road, No. 115, Wuchang District, Wuhan, Hubei Province, P.R. China. 430071

Copyright @ 2016 Medical Research Institute

XML 地图 | Sitemap 地图