IMMUNOSUPPRESSION IN PROLONGING TRANSGENE EXPRESSION: CYSTIC FIBROSIS

延长转基因表达的免疫抑制：囊性纤维化

• 批准号: 6247291
• 负责人: GARY B BASKIN
• 金额: $ 6.02万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-09 至 1998-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6247291
• 关键词: Mammalia; Primates; gene therapy; model design /development; respiratory system; virus

The genetic mutation in cystic fibrosis (CF) affects the expression of a regulator of cellular ion transport. The primary manifestations of this defect occur in the lung, liver, and pancreas. Phase-I clinical trials of CF-gene replacement, using adenoviral (AdV) vectors which are known to efficiently deliver genes to the lung and liver, have had limited success because host responses to the AdV reduce the duration of transgenic expression of CFTR. CD4+ lymphocytes are critical to these responses and depleting anti-CD4 antibody prolongs AdV expression in the lungs of rodents. We plan to test various immunosuppressive protocols in rhesus monkeys to evaluate their effect on transgene expression of AdV vectors inoculated into the lung. For this pilot project, a rhesus monkey was inoculated intrabronchially with an AdV vector containing the LacZ reporter gene. The inoculation site was biopsied 3 days later, and transgene expression was demonstrated. These preliminary results were used in a grant application, which has been partially funded by the Cystic Fibrosis Foundation. Additional studies are currently being planned.

囊性纤维化（CF）中的基因突变影响 细胞离子转运调节剂的表达。 主 这种缺陷的表现出现在肺、肝和胰腺中。 使用腺病毒（AdV）进行CF基因置换的I期临床试验 已知可将基因有效递送至肺的载体， 肝脏，已经取得了有限的成功，因为宿主对AdV的反应 减少CFTR转基因表达的持续时间。 CD4+ 淋巴细胞对这些反应至关重要， 啮齿类动物肺中的AdV抗体表达。 我们计划 在恒河猴中测试各种免疫抑制方案以评估 它们对接种到AdV载体中的转基因表达的影响 肺 在这个试验项目中， 支气管内用含有LacZ报告基因的AdV载体。 3天后对接种部位进行活组织检查，并进行转基因。 表达得到证实。 这些初步结果被用于 补助金申请，其中部分资金由囊性 纤维化基金会。 目前正在计划进行更多的研究。