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）中的遗传突变影响 细胞离子转运调节剂的表达。 主要 这种缺陷的表现发生在肺，肝脏和胰腺中。 使用腺病毒（ADV）的CF基因替换的I期临床试验 已知可以有效地将基因传递到肺的载体 肝脏，由于主机对ADV的回应而取得了有限的成功 减少CFTR的转基因表达的持续时间。 CD4+ 淋巴细胞对于这些反应和耗尽抗CD4至关重要 抗体延长啮齿动物肺中的ADV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adv载体的转基因表达的影响 肺。 对于这个飞行员项目，接种了恒河猴 与含有LACZ报告基因的ADV载体进行内介乘。 接种部位在3天后进行活检，然后转基因 表达表达。 这些初步结果用于 赠款应用程序，该应用是由囊性部分资助的 纤维化基金会。 目前正在计划其他研究。