(Taken directly from the application) The Clinical Assay Core is intended to bring state-of-the-art technology to the overall Cystic Fibrosis Gene Therapy program on our campus. The transition of experimental viral and non-viral gene transfer vectors towards preclinical testing and ultimate clinical trials requires examination of efficacy and toxicity in human cells and tissues. Gene transfer to human primary nasal airway epithelial cells, and bronchial airway epithelial cells (from bronchoscopy or other surgical remnant tissues) will be used for this purpose in Core C.
Specific Aim 1 of the Clinical Core is therefore designated to procure primary airway epithelial cells for UAB investigators, so that basic molecular virology can be translated towards improvements in gene transfer to airway epithelial cells.
Specific Aim 2 is included to provide expertise in the nasal potential difference measurement, one important endpoint in cystic fibrosis clinical trials, and also a means to understand the pathogenesis of cystic fibrosis and other metabolic diseases, such as Liddle?s syndrome.
Specific Aim 3 will bring a new and powerful CFTR imaging capability to the CF Gene Therapy Core Center using tyramide-based amplification to detect CFTR mRNA or protein. This technology is believed to be 2-3 orders of magnitude more sensitive than conventional assays of mRNA and protein localization. The method is highly specific and may be of particular value in the setting of airway gene therapy, where expression levels of CFTR mRNA or protein may be quite low. Taken together, these clinical assays will help bridge the gap between preclinical animal studies and clinical trials and will contribute to Gene Therapy Development in the CF Gene Therapy Core Center.
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