NOVEL ADENOVIRUS COMPLEXES--EFFICACY OF GENE TRANSFER TO AIRWAY EPITHELIA

新型腺病毒复合物--基因转移至气道上皮的功效

• 批准号: 6485292
• 负责人: MICHAEL J. WELSH
• 金额: $ 29万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6485292
• 关键词: Adenoviridae; biotechnology; chloride channels; cystic fibrosis; gene expression; gene therapy; genetic transduction; laboratory mouse; laboratory rabbit; neutralizing antibody; nonhuman therapy evaluation; respiratory epithelium; respiratory pharmacology; transfection /expression vector

Gene transfer to airway epithelia could provide an important new treatment for cystic fibrosis (CF) lung disease. A common problem with current vector systems is that the efficiency of gene transfer to differentiated human airway epithelia is limited. In work supported by this Program, we have investigated the advantages and limitations of adenoviral and non-viral vectors. By combining the two systems, we have utilized their unique advantages and avoided many of the limitations. In so doing, we have developed novel vector systems, including Ad:CaPi co- precipitates. This vector shows markedly enhanced gene transfer to differentiated airway epithelia. Moreover, preliminary data suggest that the Ad:CaPi co-precipitates do not produce additional toxicity. In this Project we focus on six questions. 1) How do Ad:CaP co-precipitates infect cells? 2) What properties of Ad:CaPi co-precipitates are important for gene transfer? 3) What cells are targeted by Ad:CaPi co- precipitates and other complexes? 4) Can complexes shield adenovirus from neutralizing antibodies? 5) Can other vectors, including AAV, be incorporated into CaPi co-precipitates? The results of these studies will improve our understanding of the mechanisms and barriers and gene transfer, will have application of several different vector systems, and should ultimately lead to improved gene transfer for CF airway disease.

基因转移到气道上皮细胞可能提供一个重要的新途径 治疗囊性纤维化（CF）肺病。一个常见的问题是 目前的载体系统的基因转移效率 分化的人类气道上皮是有限的。在工作支持下 这个计划，我们调查了优点和局限性 腺病毒和非病毒载体。通过结合这两个系统，我们有 利用其独特的优势并避免了许多限制。在 通过这样做，我们开发了新颖的载体系统，包括 Ad:CaPi co- 沉淀。该载体显示出显着增强的基因转移 分化的气道上皮。此外，初步数据表明 Ad:CaPi 共沉淀物不会产生额外的毒性。在这个 项目我们重点关注六个问题。 1) Ad:Cap如何共沉淀 感染细胞？ 2) Ad:CaPi 共沉淀物有什么性质 对于基因转移重要吗？ 3) Ad:CaPi co-靶向哪些细胞 沉淀物和其他复合物？ 4) 复合物可以屏蔽腺病毒吗 来自中和抗体？ 5）其他载体，包括AAV，可以吗？ 并入 CaPi 共沉淀物中？这些研究的结果 将提高我们对机制、障碍和基因的理解 转移，将应用几种不同的载体系统，并且 最终应改善 CF 气道疾病的基因转移。