title: A novel adenoviral vector carrying an all-in-one Tet-On system with an autoregulatory loop for tight, inducible transgene expression.
abstract: BACKGROUND
  One 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Laboratory of Gene Therapy, Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, Xi'an, 710062, Shaanxi, PR China. chandcn_0904@126.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Laboratory of Gene Therapy, Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, Xi'an, 710062, Shaanxi, PR China. 15829587235@163.com.
authors.forename: Dongyang
authors.initials: D
authors.lastname: Wang
authors.affiliation: College of Liberal Arts and Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. rxia2@illinois.edu.
authors.forename: Ruiting
authors.initials: R
authors.lastname: Xia
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA. q-mao@northwestern.edu.
authors.forename: Qinwen
authors.initials: Q
authors.lastname: Mao
authors.affiliation: Laboratory of Gene Therapy, Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, Xi'an, 710062, Shaanxi, PR China. hbxia2001@163.com.
authors.forename: Haibin
authors.initials: H
authors.lastname: Xia
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D005786:Gene Expression Regulation / Q000187:drug effects*; D005822:Genetic Vectors / Q000494:pharmacology; D016679:Genome, Viral; D057809:HEK293 Cells; D006801:Humans; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*; D013752:Tetracycline / Q000494:pharmacology*; D019076:Transgenes / Q000187:drug effects*
chemical_list: D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D013752:Tetracycline