Noninvasive imaging of therapeutic gene expression using a bidirectional transcriptional amplification strategy.

ABSTRACT: Promoters that limit transgene expression to tumors play a vital role in cancer gene therapy. Although tumor specific, the human Survivin promoter (pSurv) elicits low levels of transcription. A bidirectional two-step transcriptional amplification (TSTA) system was designed to enhance expression of the therapeutic gene (TG) tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL or TR) and the reporter gene firefly luciferase (FL) from pSurv. An adenoviral vector carrying the enhanced targeting apparatus (Ad-pSurv-TR-G8-FL) was tested for efficiency and specificity of gene expression in cells and in living animals. Compared to the one-step systems (Ad-pSurv-FL or Ad-pSurv-TR), the bidirectional TSTA system showed tenfold higher expression of both the therapeutic and the reporte

SUBMITTER: Ray S 

PROVIDER: S-EPMC3195556 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature