A complex adenovirus vector that delivers FASL-GFP with combined prostate-specific and tetracycline-regulated expression

Semyon Rubinchik, Danher Wang, Hong Yu, Fan Fan, Min Luo, James S. Norris, Jian yun Dong

Research output: Contribution to journalArticlepeer-review


Cell-type-restricted transgene expression delivered by adenovirus vectors is highly desirable for gene therapy of cancer, as it can limit cytotoxic gene expression to tumor cells. However, many tumor- and tissue-specific promoters are weaker than the constitutively active promoters and are thus less effective. To combine cell-type specificity with high-level regulated transgene expression, we have developed a complex adenoviral vector. We have placed the tetracycline transactivator gene under the control of a prostate-specific ARR2PB promoter, and a mouse Tnfsf6 (encoding FASL)-GFP fusion gene under the control of the tetracycline responsive promoter. We have incorporated both expression cassettes into a single construct. We show that FASL-GFP expression from this vector is essentially restricted to prostate cancer cells, in which it can be regulated by doxycycline. Higher levels of prostate-specific FASL-GFP expression were generated by this approach than by driving the FASL-GFP expression directly with ARR2PB. More FASL-GFP expression correlated with greater induction of apoptosis in prostate cancer LNCaP cells. Mouse studies confirmed that systemic delivery of both the prostate-specific and the prostate-specific/tet-regulated vectors was well tolerated at doses that were lethal for FASL-GFP vector with CMV promoter. This strategy should be able to improve the safety and efficacy of cancer gene therapy using other cytotoxic genes as well.

Original languageEnglish (US)
Pages (from-to)416-426
Number of pages11
JournalMolecular Therapy
Issue number5
StatePublished - 2001
Externally publishedYes


  • Combined regulation
  • Expression amplification
  • Prostate-specific promoter
  • Tetracycline expression system

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery


Dive into the research topics of 'A complex adenovirus vector that delivers FASL-GFP with combined prostate-specific and tetracycline-regulated expression'. Together they form a unique fingerprint.

Cite this