Several groups have modified adenoviral vector broad tropism and have achieved a targeted gene expression in somatic tissues using a variety of approaches including modification of viral structural proteins and inclusion of tissue-specific promoters. 1-9 However, the finding that the adenoviral background can cause either loss of tissue specificity [10][11][12] or down-regulation of promoters used to drive transgene expression 12 has limited the application of the last approach.Transcriptional interference mediated by several ciselements, mainly located on the left end of the adenovirus chromosome, appears to be accountable for this phenomenon (Figure 1a). The inverted terminal repeat (ITR) contains redundant binding sites for cellular factors and stimulates transcription from E1 and E4 genes. [13][14][15] The bipartite E1A enhancer trans-activates the E1A gene through the cellular protein EF-1A and controls the expression of the early genes after infection. 16,17 The promoter for the intermediate transcript pIX is situated just downstream of the canonical E1 cloning site for expression cassettes. Since some of these elements overlap with the viral origin of replication and the packaging signal, they cannot be deleted or inactivated. Thus other strategies based on the use of transcription modulators have been developed to achieve targeted gene delivery.