GENE THERAPY FOR AUTOIMMUNE ARTHRITIS

基因治疗提供了一种可能的手段，提供抗炎生物制剂，如白细胞介素-10，长期治疗自身免疫性关节炎。腺病毒载体介导的基因治疗允许这些治疗性蛋白质的高表达。然而，这种表达通常是短暂的，部分是由于病毒载体和/或所表达的转基因蛋白的免疫原性。 在前两个具体目标中概述的研究将确定是否可以利用经工程改造以降低对腺病毒载体和/或转基因蛋白产物的免疫原性的腺病毒载体来延长转基因表达。第三个具体目标是在CIA小鼠模型系统中功能性测试这些载体对自身免疫性关节炎的作用。本研究将为自身免疫性关节炎基因治疗的进一步发展提供有价值的数据。

Gene therapy provides a possible means to deliver anti-inflammatory biological agents, such as interleukin-10, for long-term treatment of autoimmune arthritis. Adenoviral vector mediated gene therapy allows for high expression of these therapeutic proteins. However, this expression is normally short-lived, in part due to immunogenicity of the viral vector and/or transgenic protein being expressed. Studies outlined in the first two specific aims will determine whether transgene expression can be prolonged utilizing adenoviral vectors engineered to reduce immunogenicity to the adenoviral vector and/or transgenic protein product. The third specific aim functionally tests these vectors in the CIA mouse model system for their effects on autoimmune arthritis. The studies outlined in this proposal will provide valuable data in furthering the development of gene therapy for autoimmune arthritis.