A modification of the existing INSM1
promoter region has been discovered that incorporated
DNA elements that
silence expression of neuronal genes in non-neuronal cells and that has increased the effectiveness and safety of using the INSM1
promoter for tumor treatment. One modification was addition of one or two tandem copies of neuronal restrictive silencer elements (NRSEs) derived either from the mouse
nicotinic acetylcholine receptor (nAChR) or the rat superior cervical
ganglion 10 (SCG10) promoters. These NRSEs were placed in the expression construct either directly upstream or downstream of the INSM1
promoter sequence. The most effective expression construct was the nAChR NRSE element positioned downstream of the INSM1 promoter. This expression construct increased the
tissue specificity of the INSM1 promoter without a significant decrease in its activity. In addition, the modified INSM1 promoter was placed into a
viral vector, adenovirus 5. Constructs with an insulator element, the chicken HS4 β-
globin insulator element, with the INSM1 promoter was shown to decrease the interference of the viral
genome on its expression. Constructs have been made that do not decrease the INSM1
promoter activity but significantly augment the tumor specificity of the promoter. Linking the construct to a
reporter gene allowed for detection of the placement of the
viral vector, and this detection can be used for diagnosing or locating
neuroendocrine tumors.