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可以提供重要的新 治疗囊性纤维化（CF）肺部疾病。一个常见的问题 当前的向量系统是基因转移到 分化的人类气道上皮受到限制。在工作中支持 该计划，我们调查了 腺病毒和非病毒载体。通过结合两个系统，我们有 利用了它们的独特优势，并避免了许多局限性。在 因此，我们已经开发了新颖的向量系统，包括AD：CAPI共同 沉淀。该载体显示出明显增强的基因转移到 区分气道上皮。此外，初步数据表明 AD：CAPI共归因不产生其他毒性。在这个 项目我们专注于六个问题。 1）AD如何：CAP共同授权 感染细胞？ 2）AD的属性：CAPI共同授权是 对于基因转移很重要？ 3）什么细胞针对AD：CAPI共同 沉淀和其他复合物？ 4）可以复合盾牌腺病毒 来自中和抗体？ 5）其他媒介（包括AAV）可以 纳入CAPI共同授权？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，将应用几个不同的向量系统，并且 最终应导致CF气道疾病的基因转移改善。