Evaluation of promoter strength for hepatic gene expression in vivo following adenovirus-mediated gene transfer

Gene Ther. 1996 Sep;3(9):802-10.


Transgene expression in studies of both gene function and gene therapy may be assisted considerably through the use of transcriptional regulatory elements which permit high-level, and/or tissue-specific gene expression. We have therefore evaluated the transcriptional activities of a series of viral and cellular enhancer/promoter elements, both in vitro and in vivo. The five enhancer/promoter elements showing either high-level or hepatocyte-specific expression following transient transfection into hepatoma cells were incorporated into recombinant adenoviruses expressing human alpha 1-antitrypsin (hAAT) for in vivo studies in the liver of immunodeficient and immunocompetent mice. The human elongation factor 1 alpha gene promoter produced 2 mg/ml serum level of hAAT, which is physiologic in humans and will be therapeutic for patients with AAT deficiency. This and all other enhancer/promoters except that of the CMV-IE gene yielded persistent hAAT expression in SCID mice. These findings demonstrate that adenovirus vectors provide an effective system for studies designed to evaluate enhancer/promoter activities in vivo. Several of the enhancer/promoters examined in this study will have significant utility in adenovirus-mediated gene therapy for alpha 1-antitrypsin deficiency and other genetic disorders.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviruses, Human / genetics*
  • Animals
  • Carcinoma, Hepatocellular
  • DNA, Viral / analysis
  • Enhancer Elements, Genetic / genetics
  • Female
  • Gene Expression*
  • Gene Transfer Techniques*
  • Genetic Vectors / genetics
  • Humans
  • Liver / metabolism*
  • Liver Neoplasms
  • Mice
  • Mice, Inbred C57BL
  • Mice, SCID
  • Organ Specificity
  • Peptide Elongation Factor 1
  • Peptide Elongation Factors / genetics
  • Promoter Regions, Genetic / genetics*
  • RNA, Messenger / analysis
  • Tumor Cells, Cultured
  • alpha 1-Antitrypsin / analysis
  • alpha 1-Antitrypsin / genetics


  • DNA, Viral
  • Peptide Elongation Factor 1
  • Peptide Elongation Factors
  • RNA, Messenger
  • alpha 1-Antitrypsin