Recombinant Sendai viruses expressing different levels of a foreign reporter gene

Sendai virus (SeV) is an enveloped virus with a nonsegmented negative strand RNA genome. The recovery of infectious virus from cDNA and generation of recombinant SeV carrying a foreign gene at the promoter proximal position has been demonstrated. In this study, we constructed a series of recombinant SeVs carrying a reporter human secreted alkaline phosphatase (SEAP) gene at each viral gene junction or the 5' distal end in order to measure the expression level of the foreign gene. We demonstrated that there was a gradient in the reporter gene expression level that depended on location, due to the polarity of transcription. In contrast, the growth and final titers of these recombinant viruses showed an opposite gradient to the foreign gene expression level. This suggests the potential for matching therapeutic gene expression level to individual therapy programs by changing the position of the foreign gene when SeVs are used as vectors for human gene therapy. (C) 2002 Elsevier Science B,V. All rights reserved.