title: Efficient adenovirus-mediated gene transfer to gastric tissue by oral administration.
abstract: BACKGROUND
  Recombinant adenoviruses (rAd) are well-characterized viral vectors and have been studied in many human diseases. However, there are no detailed methods for transferring genes to the stomach using rAd.
  
  
  METHODS
  Gastric epithelial cells were infected with rAd encoding green fluorescence protein (AdGFP) for different times, or with AdGFP that had been incubated in artificial gastric juice at different pH values for 1 h. Gene expression was detected by fluorescence microscope and flow cytometry. Mice were infected via oral administration with rAd encoding red fluorescence protein and beta-galactosidase (AdRFP-lacZ) or rAd encoding mouse interleukin-17 (AdmIL-17), and tissues were collected at the indicated times after infection. LacZ expression in different tissues was detected by X-gal staining and IL-17 expression in the stomach was assessed by the real-time polymerase chain reaction and an enzyme-linked immunosorbent assay. Inflammation in the stomach was also assessed.
  
  
  RESULTS
  rAd could infect the gastric epithelial cells and tolerate pH 5 for 1 h in vitro. Adenovirus-mediated genes were specifically expressed in the gastrointestinal tract and transgene expression persisted in gastric tissue for up to 7 days after oral administration of AdRFP-lacZ. Oral administration of AdmIL-17 induced mIL-17 expression in gastric tissue at the mRNA and protein levels and protein level peaked on day 5 post-infection. IL-6, a target protein of IL-17, and gastric inflammation also increased in AdmIL-17-infected mice.
  
  
  CONCLUSIONS
  The present study has established a detailed method for transferring adenovirus-mediated gene to the stomach, which may provide a valuable approach for gene therapy or the study of the basic biology of gastric diseases.
authors.affiliation: Department of Clinical Microbiology and Immunology, Third Military Medical University, Chongqing, China.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Liu
authors.forename: Yun
authors.initials: Y
authors.lastname: Shi
authors.forename: Jin-Yu
authors.initials: JY
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Ke-Ran
authors.initials: KR
authors.lastname: Jia
authors.forename: Xu-Hu
authors.initials: XH
authors.lastname: Mao
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Chao
authors.initials: C
authors.lastname: Wu
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Zhang
authors.forename: Wei-Ying
authors.initials: WY
authors.lastname: Zhou
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
authors.forename: Quan-Ming
authors.initials: QM
authors.lastname: Zou
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000284:Administration, Oral; D000818:Animals; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D041981:Gastrointestinal Tract; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D020381:Interleukin-17 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D007763:Lac Operon / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000821:virology; D019076:Transgenes / Q000502:physiology; D001616:beta-Galactosidase / Q000235:genetics; D000097573:Red Fluorescent Protein
chemical_list: D020381:Interleukin-17; D015850:Interleukin-6; D008164:Luminescent Proteins; D012333:RNA, Messenger; D001616:beta-Galactosidase; D000097573:Red Fluorescent Protein