报告题目：Novel Developments in Lung Gene Therapy

报告人：   Jim Hu, Ph.D.
                 Professor, Department of Laboratory Medicine and Pathobiology
                 University of Toronto  
主持人：   冯新华  教授

Abstract：

Despite the early hype in gene therapy, there are still major obstacles to translating genetic discoveries into clinical applications. These obstacles include innate and immune barriers to vector delivery, toxicity of vectors and the lack of sustained therapeutic gene expression. To overcome these obstacles, my research team has been developing novel gene expression cassettes and gene therapy vectors to improve therapeutic gene expression and to reduce host immune responses against gene therapy vectors. In addition, we have been developing novel delivery methods to achieve robust levels of transgene expression in small and large animal models. We have been using cystic fibrosis lung disease as an example to demonstrate the safety and efficiency of our technology. Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Although multiple organs and tissues are affected in CF patients, the major mortality and morbidity are due to lung failure. Gene therapy became an attractive therapeutic strategy because the lung airway is accessible to gene vectors. We have shown that our gene delivery system can be used to deliver human CFTR gene to CF knockout mice to protect them from acute lung infection. We have developed a strategy for vector re-administration through transient immunosuppression of the host immune system. We have recently shown that our vector system and delivery methods allow safe and effective delivery of genes to the pig lungs. These techniques can be adapted for gene therapy targeting other diseases, such as cancers.