Derivation of Dendritic Cell-Specific Adenovirus Vectors

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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