TARGETING ADENOVIRUS TO THE INTESTINE

将腺病毒靶向肠道

• 批准号: 6413555
• 负责人: JOEL R CHAMBERLAIN
• 金额: $ 1.65万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6413555
• 关键词: Adenoviridae; cell line; epithelium; host organism interaction; intestines; organ culture; transfection /expression vector; virus infection mechanism; virus protein; virus receptors

Advances in gene delivery, including development of synthetic and viral vectors, has provided a means of manipulation of the cell for study both in vitro and in vivo. Recent focus on specific cell targeting to reduce viral particle manipulation of the cell for study both in vitro and in vivo. Recent focus on specific cell type targeting to reduce viral particle load and immune induction has led to the development of tools aimed at gene delivery to defined sites in the whole animal. In particular, the adenoviral vector system has received attention as a prominent candidate for use in treating disease and inborn errors of metabolism. Previous efforts to target adenoviral vectors to specific cell types have had limited success. Most of the human adenoviruses use the Coxsackie- Adenovirus receptor (CAR) for cell attachment. CAR is found on a wide variety of cells in low number. Contact between the adenovirus and CAR is mediated by a single type of viral fiber protein. The exceptions, subgroups B and F, are thought to make cell contact through unidentified receptors, Subgroup F adenoviruses display a strong tropism for intestinal epithelial cells which are not efficiently infected by the commonly used Ad2 and Ad5 serotypes. This project will generate Ad5 vectors displaying the subgroup F virus, Ad41, surface fiber proteins. The subgroup F viruses possess two different fiber proteins unlike other subtypes that possess only one. The goal of this proposal is to understand the relative contributions of each of the two Ad41 fiber proteins to intestinal cell specificity by placing the fiber proteins in separate virions. In addition to CAR, the unknown receptor for Ad41 will be identified using the pseudotyped virus. Together these studies will lead to advances in virology and will provide a first step toward developing gene therapy for diseases of the bowel.

基因递送的进步，包括合成和病毒载体的发展，为在体外和体内进行研究提供了一种操纵细胞的手段。最近关注特定细胞靶向，以减少细胞的病毒颗粒操纵，以在体外和体内研究。最近关注特定细胞类型靶向，以减少病毒颗粒负荷和免疫诱导，导致了旨在基因递送到整个动物定义位点的工具的开发。特别是，腺病毒媒介系统已成为用于治疗疾病和天生代谢错误的重要候选人。以前将靶向腺病毒载体靶向特定细胞类型的努力取得了有限的成功。大多数人类腺病毒使用Coxsackie-腺病毒受体（CAR）进行细胞附着。汽车在数量较低的各种细胞上发现。腺病毒和汽车之间的接触是由一种类型的病毒纤维蛋白介导的。异常，亚组B和F通过未鉴定的受体使细胞接触，亚组F腺病毒对肠上皮细胞表现出强大的向热，而肠道上皮细胞没有被常用的AD2和AD5血清型有效地感染。该项目将生成AD5矢量，以显示亚组F病毒，AD41，表面纤维蛋白。与其他仅具有一种的亚型不同，亚组F病毒具有两种不同的纤维蛋白。该提案的目的是通过将纤维蛋白放置在单独的病毒体中，了解两个AD41纤维蛋白中每一个对肠细胞特异性的相对贡献。除了CAR之外，还将使用伪型病毒鉴定出AD41的未知受体。这些研究将共同​​导致病毒学的进步，并将为开发肠道疾病的基因疗法提供第一步。