ROLE OF CPG MOTIFS IN PLASMID DNA AS A BARRIER TO GENE TRANSFER

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cystic fibrosis is an autosomal recessive genetic disorder in which the pathogenetic defect, dysfunction or loss of the c1-channel Cystic Fibrosis Transmembrane Regulator (CFTR) has been identified. Gene therapy for this disease is attractive because the affected organ most often responsible for death (the lung) is accessible for gene therapy. Despite some inefficiency in gene delivery, liposome-mediated gene transfer using plasmid vectors has significant potential for correction of the CFTR defect in humans in vivo. Alveolar macrophages can be a source of toxicity to the subject in gene therapy trials. Alveolar macrophages are the most numerous inflammatory cells in the airway. As antigen presenting as well as phagocytic cells, they are a central player in the innate defense system of the lung and have evolved to prevent infection from inhaled bacteria or other pathogens. This study is investigating how vectors are used in gene therapy and how they interact with these lavage cells or products of the lavage cells to impair gene therapy. This will allow these investigators to study in vitro the method of relating action of alveolar macrophages with other cells and gene therapy. They hypothesize that gene delivery, liposome-mediated gene transfer using plasmid vectors, has significant potential for correction of the CFTR defect in humans in vitro.