Cystic Fibrosis (CF), being an autosomal recessive genetic disorder with a single gene defect, seemed an ideal target for gene therapy. Targeted delivery of the therapeutic gene, CFTR to airway epithelium should restore normal function. Previously, a peptide ligand (C105Y) for sec-R receptor was labeled with radio-iodide (on Tyr residue) for imaging the dynamics of delivered therapeutic gene complexes to the airways (see the diagram below). It is crucial to monitor the gene therapy by tracing genes: how many are actually expressed; and how long the expression lasts. A dual reporter gene approach was adopted in this project to image gene expression in the lungs of CF knockout mice. HSV1-tk and luc were compacted using ploy-K, and mixed in equal molar for delivery. In addition, saline was delivery to another group of mice, as a control. Both intra-nasal and intra-tracheal administration methods were tested in this study. Data from tissue assays of lung activity agreed nicely upon examination of two imaging modalities, gamma scintigraphy for HSV1-tk using [I-125]-FIAU & bioluminescence imaging for luc using luciferin.
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