title: Targeted genome correction by a single adenoviral vector simultaneously carrying an inducible zinc finger nuclease and a donor template.
abstract: Zinc finger nuclease (ZFN) technology, which can be used to induce targeted genome correction in the presence of a DNA donor template, is becoming an attractive strategy for treating monogenic diseases. This strategy requires efficient delivery of ZFN and donor template into cells, ideally, in a single viral vector to achieve efficient genome editing and to avoid unwanted mutagenesis. In this study, we successfully produced a single adenoviral (Ad) vector with high titer that carried a ZFN expression cassette and a donor template simultaneously. We then demonstrated that this single Ad system could mediate efficient site-specific genome correction in vitro and ex vivo. The gene correction efficiency of the single Ad was significantly higher than that of the double Ad system. This novel vector will be a promising ZFN and donor delivery system for treatment of monogenic diseases.
authors.affiliation: Co-Innovation Center for Qinba Regions' Sustainable Development, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, Shaanxi, PR China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Co-Innovation Center for Qinba Regions' Sustainable Development, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, Shaanxi, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Co-Innovation Center for Qinba Regions' Sustainable Development, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, Shaanxi, PR China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Co-Innovation Center for Qinba Regions' Sustainable Development, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, Shaanxi, PR China.
authors.forename: Dongyang
authors.initials: D
authors.lastname: Wang
authors.affiliation: Co-Innovation Center for Qinba Regions' Sustainable Development, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, Shaanxi, PR China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Ji
authors.affiliation: Co-Innovation Center for Qinba Regions' Sustainable Development, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, Shaanxi, PR China. Electronic address: hbxia2001@163.com.
authors.forename: Haibin
authors.initials: H
authors.lastname: Xia
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Qinwen
authors.initials: Q
authors.lastname: Mao
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D002460:Cell Line; D003851:Deoxyribonucleases / Q000235:genetics*; D005822:Genetic Vectors; D016678:Genome; D006801:Humans; D016296:Mutagenesis; D016335:Zinc Fingers
chemical_list: D003851:Deoxyribonucleases
keywords: Adenoviral vector; Genome editing; Homologous recombination; Site-specific integration; Zinc finger nuclease