A small chimeric promoter for high prostate-specific transgene expression from adenoviral vectors

Prostate. 2007 Jun 1;67(8):829-39. doi: 10.1002/pros.20560.

Abstract

Background: Specificity of transgene expression is important for safety during gene therapeutical applications. For prostate cancer, transcriptional targeting has been applied but was hampered by loss of specificity and low activity. We constructed a small chimeric promoter for high and prostate-specific transgene expression from adenoviral vectors.

Methods: A chimeric promoter, composed of the prostate-specific antigen (PSA) enhancer and the rat probasin promoter, was cloned into an adenoviral vector and its activity was compared to vectors containing conventional prostate-specific promoters and the constitutive Cytomegalovirus (CMV) promoter in in vitro and in vivo prostate cancer models.

Results: The chimeric PSA-probasin promoter was the most active prostate-specific promoter reaching up to 20% of CMV promoter activity while maintaining prostate-specificity.

Conclusions: The chimeric PSA-probasin promoter is a small promoter that can be utilized in viral vectors for high prostate-specific transgene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / therapy*
  • Adenoviridae / genetics
  • Androgen-Binding Protein / genetics
  • Animals
  • Cell Line, Tumor
  • Cytomegalovirus / genetics
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Microscopy, Fluorescence
  • Plasmids / genetics
  • Promoter Regions, Genetic*
  • Prostate-Specific Antigen / genetics
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / therapy*
  • Recombinant Fusion Proteins / genetics
  • Transgenes*

Substances

  • Androgen-Binding Protein
  • Recombinant Fusion Proteins
  • probasin
  • Prostate-Specific Antigen