Avian transgenesis via site-directed integration

通过定点整合进行鸟类转基因

• 批准号: 6736593
• 负责人: Alex Jordan Harvey
• 金额: $ 9万
• 依托单位: SYNAGEVA BIOPHARMA CORPORATION
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-15 至 2004-06-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6736593
• 关键词: biotechnology; chick embryo; chickens; gene delivery system; genetically modified animals; integrase; method development; protein biosynthesis; protein structure function; quail; transfection

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.

描述(由申请人提供)： 这个SBIR项目描述了一种新的方法来创造转基因家禽，这种家禽将在它们的鸡蛋中产生生物制药蛋白。家禽，包括鸡和鹌鹑，能够以相对较低的成本在鸡蛋中产生大量蛋白质。我们试图利用这种能力来合成大量所需的药用蛋白质，例如人源化的单抗。在鸟类中转基因的效率非常低，特别是具有大量转基因的鸟类。我们建议通过使用整合促进酶来克服这一障碍，这种酶能够高效地重组特定的DNA序列。在本项目的第一阶段，我们将对整合促进酶的活性进行优化，使其适用于早期禽类胚胎。我们还将评估大型转基因(即高达190千碱基)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用蛋白的转基因插入家禽基因组，并由蛋清特异性启动子驱动。这项新技术将加快创造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。