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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。囊性纤维化是一种常染色体隐性遗传疾病，其中已确定c1通道囊性纤维化跨膜调节因子（CFTR）的致病缺陷、功能障碍或缺失。这种疾病的基因治疗是有吸引力的，因为受影响的器官最经常负责死亡（肺）是基因治疗。尽管在基因递送中存在一些效率低下的情况，但使用质粒载体的脂质体介导的基因转移具有在体内校正人类CFTR缺陷的显著潜力。肺泡巨噬细胞可能是基因治疗试验中受试者的毒性来源。肺泡巨噬细胞是气道中数量最多的炎性细胞。作为抗原呈递细胞和吞噬细胞，它们是肺先天防御系统的核心参与者，并且已经进化为防止吸入细菌或其他病原体的感染。本研究旨在探讨载体如何用于基因治疗，以及它们如何与这些灌洗液细胞或灌洗液细胞的产物相互作用以损害基因治疗。这将使这些研究人员能够在体外研究肺泡巨噬细胞与其他细胞和基因治疗相关的方法。他们假设基因递送，使用质粒载体的脂质体介导的基因转移，具有在体外纠正人类CFTR缺陷的显著潜力。

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.