? ? This SBIR project describes a novel method to create transgenic poultry that will produce biopharmaceutical proteins in their eggs. Poultry, including chickens and quail, are able to produce large amounts of protein in their eggs at relatively low cost. We seek to harness this capability to synthesize pharmaceutical proteins, such as humanized monoclonal antibodies, that are needed in large amounts. The efficiency of transgenesis in avians, particularly with large transgenes, is exceedingly low. We propose here to overcome this hurdle by the use of integration-promoting enzymes, which are able to recombine specific DNA sequences with a high efficiency. In Phase I of this project we will optimize the activity of integration promoting enzymes so that it is applicable in the early avian embryo. We will also evaluate the integration of large transgenes (i.e. up to 190 kilobasepairs), including bacterial artificial chromosomes. In Phase II of this project, the integration-promoting enzymes will be used to insert transgenes encoding pharmaceutical proteins, and driven by egg white specific promoters, into the genome of poultry. This novel technology will expedite the creation of poultry that can produce pharmaceuticals, thereby facilitating drug development, enhancing clinical trials and lowering the cost of pharmaceuticals. ? ?
