Basic science discoveries have led to the development of a series of human biotherapeutic drugs for the treatment of cancer and HIV as well as many other diseases. Currently there are over 400 drugs in clinical trials just for the first two diseases. The current biotherapeutics' manufacturing platforms have not kept pace resulting in a dramatic rise in treatment cost and more importantly unmet therapeutic needs. Avian transgenesis is an emerging technology that has the potential to radically increase the US manufacturing capacity of biotherapeuticals. AviGenics, Inc proposes a novel recombinant protein manufacturing platform that will allow us to express human therapeutic molecules in the egg white of hens. OBJECTIVES: The specific objective of this proposal is to develop a method to introduce large transgenes or multiple large transgenes into the avian genome. The long term objective of this project is to apply this technology to develop transgenic flocks of poultry which produce biopharmaceutical proteins in their eggs. An efficient method for generation of transgenic flocks would have applications in fields as varied as production of human therapeutic proteins and basic research on vertebrate gene function, enhancement of agronomic traits such as increase feed to gain ratios and production of disease resistant animals for both natural and bioterror-derived disease outbreaks APPROACH: The overall goal of this project is to create a Transchromosomic production flock hosting an expression vector comprising an oviduct specific promoter driving the expression of a human therapeutic molecule (OSP/HTM). Phase one goals include: 1. Generation and characterization of 3 Artificial Chromosome clones hosting the OSP/HTM vector. 2. Injection and generation of founder birds (G0) hosting the OSP/HTM vector 3. Characterization of G0 founders
