A novel adenoviral vector carrying an all-in-one Tet-On system with an autoregulatory loop for tight, inducible transgene expression

BMC Biotechnology

Research Article

Ruiting Xia¹  Qinwen Mao²  Dongyang Wang³  Haibin Xia³  Hao Chen³ 

[1] College of Liberal Arts and Sciences, University of Illinois at Urbana-Champaign, 61801, Urbana, IL, USA;Department of Pathology, Northwestern University Feinberg School of Medicine, 60611, Chicago, IL, USA;Laboratory of Gene Therapy, Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, 710062, Xi’an, Shaanxi, PR China;

关键词: Adenoviral vector;    Tet-On;    Transgene;    Inducible vector;    Gene therapy;   

DOI  :  10.1186/s12896-015-0121-4

 received in 2014-09-27, accepted in 2015-01-30,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundOne of the most commonly used vectors for gene therapy is the adenoviral vector; its ability to tightly regulate transgene expression is critical for optimizing therapeutic outcomes. The tetracycline-regulated system (especially the Tet-On system) for gene expression is one of the most valuable tools for controlling gene expression. The major problem of an adenoviral vector carrying a Tet-On system is suboptimal regulation of transgene expression.ResultsWe constructed a single adenoviral vector carrying in its E1 region a novel “all-in-one” Tet-On system with an autoregulatory loop. This system had improved Dox-inducible gene expression in terms of low basal expression, high induced expression and high responsiveness to Dox. To our knowledge, this is the first reported adenovirus-based, all-in-one Tet-On system with an autoregulatory loop inserted into a single region of adenoviral genome. This system was further tested by inducible expression of soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL). The adenovirus that expressed soluble TRAIL under the control of this novel Tet-On system showed tumor-derived cells inhibitory activity in SW480 cells only under induced conditions.ConclusionsOur novel, single adenoviral vector carrying in its E1 region an all-in-one Tet-On system with an autoregulatory loop displayed tight regulation of transgene expression in vitro. This system has great potential for a variety of applications, including gene therapy and the study of gene function.

【 授权许可】

Unknown   
© Chen et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.