Derivation of Dendritic Cell-Specific Adenovirus Vectors

描述(申请人提供)：本研究的长期目标 该项目旨在开发一种新的、有效的人类转导策略 树突状细胞(DC)用于基因抗肿瘤免疫。至 为了实现这一目标，我们将开发一种基于腺病毒(Ad)的基因递送 一种能够高效和特异地利用 CD4OL-CD4O相互作用的自然机制。因此，我们将开发一种 一种新型的病毒载体，能够诱导对AFP的有效免疫应答 载体编码的免疫原通过有效的DC转导。第一个具体 目的是设计一种融合结构的重组蛋白嵌合体 Ad5纤维和CD4OL分子的成分，并具有关键特征 两种亲本蛋白质的结合。第二个具体目标是展示其可行性 将纤维-CD4OL嵌合蛋白掺入有活力的Ad病毒粒子中 并展示了这些病毒载体实现CD40特异性的能力 基因转移。实验计划将包括对纤维-CD4OL进行建模 嵌合蛋白，广泛的结构和功能表征 这些蛋白在大肠杆菌中表达，将这些嵌合体掺入Ad. 病毒粒子和证明这些病毒载体的DC特异性。这个 该项目的目标是开发能够靶向 树突状细胞(DC)通过CD-40受体。 建议的商业应用： 不可用

DESCRIPTION (provided by applicant): The long-range goal of this research project is to develop a novel and effective strategy for transduction of human dendritic cells (DC) for the purposes of genetic anti-tumor immunization. To accomplish this goal, we will develop an adenovirus(Ad)-based gene delivery system capable of efficient and specific transduction of DC by utilizing the natural mechanism of CD4OL-CD4O interaction. As a result, we will develop a novel viral vector capable of eliciting a potent immune response to a vector-encoded immunogen by efficient transduction of DC. The first specific aim is to design a recombinant protein chimera incorporating structural elements of the Ad5 fiber and CD4OL molecules, and possessing the key features of both parental proteins. The second specific aim is to show the feasibility of incorporation of the fiber-CD4OL chimeric proteins into viable Ad virions and demonstrate the ability of these viral vectors to achieve CD40-specific gene transfer. The experimental plan will include modeling of the fiber-CD4OL chimeric proteins, extensive structural and functional characterization of these proteins expressed in E.coli, incorporation of these chimeras into Ad virions and demonstration of the DC-specificity of these viral vectors. The goal of this project is to develop adenoviral vectors that can target the dendritic cells (DC) through CD-40 receptor. PROPOSED COMMERCIAL APPLICATION: Not available