Avian transgenesis via site-directed integration

描述（由申请人提供）： 该SBIR项目描述了一种新的方法，以创建转基因家禽，将产生生物药物蛋白质在他们的鸡蛋。家禽，包括鸡和鹌鹑，能够以相对较低的成本在鸡蛋中生产大量蛋白质。我们试图利用这种能力来合成大量需要的药物蛋白质，如人源化单克隆抗体。禽类的转基因效率，特别是大的转基因，非常低。我们在这里建议通过使用整合促进酶来克服这一障碍，这些酶能够以高效率重组特定的DNA序列。在本项目的第一阶段，我们将优化整合促进酶的活性，使其适用于早期鸟类胚胎。我们还将评估大型转基因（即多达190个转基因酶对）的整合，包括细菌人工染色体。在该项目的第二阶段，整合促进酶将用于将编码药物蛋白的转基因插入家禽基因组中，并由鸡蛋白色特异性启动子驱动。这项新技术将加快培育能够生产药物的家禽，从而促进药物开发，加强临床试验并降低药物成本。

DESCRIPTION (provided by applicant): 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.