BACKGROUND: Inefficiency, aspecificity and @entity137 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 @entity1 situation. We present a clinically relevant tissue slice technology to preclinically test improved vector characteristics. METHODS: Slices were prepared from @entity35 , @entity19 and @entity1 liver samples and from @entity5 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 @entity35 liver slices, we demonstrate efficient knob-mediated adenoviral infectivity. A favorable @entity5 -on/liver-off profile, resembling in vitro and @entity19 in vivo data, was shown for a @entity5 -specific transcriptionally retargeted adenovirus by infecting slices prepared from @entity5 or liver tissue. Similar liver-off data were found for @entity19 , @entity35 and @entity1 samples (over 3-log lower activity of the @entity5 -specific promoter compared to cytomegalovirus ( @entity2834 )). More importantly, we show that this technology when applied to @entity1 livers is a powerful tool to determine aspecific replication of oncolytic viruses in liver tissue. A 2- to 6-log reduction in viral replication was observed for a @entity5 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 @entity1 tissue.

An ex vivo XXXX model system to evaluate specificity of replicating and non-replicating gene therapy agents.

@entity1 :: ('9606', 'Species') :: ['human'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumor-specific oncolytic virus'] @entity2834 :: ('12305', 'Species') :: ['CMV'] @entity35 :: ('10116', 'Species') :: ['rat']
@entity1 :: (9606,Species) :: ['human']
