WS09.04 Enhancement of channel activity of the CFTR protein delivered via gene therapy vectors

Abstract

Objectives: The advancements in developing CFTR-targeted drugs offer effective treatments for most cystic fibrosis patients. However, there is still a small portion of patients who do not respond to the new drugs. In addition, it is still unclear whether the drugs can maintain the lung function of the patients in long term. Thus, other novel therapeutic strategies should be investigated. Using gene therapy to express a copy of functional CFTR gene in CF cells is an attractive strategy. Currently, one of the major challenges is how to deliver enough functional CFTR protein to CF lungs to achieve therapeutic effects. Our group has been using a gene expression cassette based on the human cytokeratin 18 (K18) gene promoter to express the CFTR gene. Since K18 gene expression has been reported to be enhanced by sodium butyrate, here we are examining whether CFTR expression can be further enhanced following vector delivery to CF cells.