27 Scopus citations


Background: Inefficiency, aspecificity and toxicity of gene transfer vectors hamper gene therapy from showing its full potential. On this basis significant research currently focuses on developing vectors with improved infection and/or expression profiles. Screening assays with validity to the clinical context to determine improved characteristics of such agents are not readily available since this requires a close relationship to the human situation. We present a clinically relevant tissue slice technology to preclinically test improved vector characteristics. Methods: Slices were prepared from rat, mouse and human liver samples and from tumor tissue. Specificity of gene expression and replication was determined by infecting target and non-target tissue slices with transcriptionally retargeted adenoviruses and oncolytic viruses. Results: Using rat liver slices, we demonstrate efficient knob-mediated adenoviral infectivity. A favorable tumor-on/liver-off profile, resembling in vitro and mouse in vivo data, was shown for a tumor-specific transcriptionally retargeted adenovirus by infecting slices prepared from tumor or liver tissue. Similar liver-off data were found for mouse, rat and human samples (over 3-log lower activity of the tumor-specific promoter compared to cytomegalovirus (CMV)). More importantly, we show that this technology when applied to human livers is a powerful tool to detennine aspecific replication of oncolytic viruses in liver tissue. A2- to 6-log reduction in viral replication was observed for a tumor-specific oncolytic virus compared to the wild-type adenovirus. Conclusions: The precision-cut tissue slice technology is a powerful method to test specificity and efficiency of gene transfer as well as of viral replication using human tissue.

Original languageEnglish
Pages (from-to)35-41
Number of pages7
JournalJournal of Gene Medicine
Issue number1
StatePublished - Jan 2006


  • Carcinoma
  • Oncolysis
  • Retargeting
  • Toxicity
  • Virotherapy


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