Oviduct locus BACs for expression of bio-therapeutics

用于表达生物治疗药物的输卵管位点 BAC

• 批准号: 6834199
• 负责人: MARK C. LEAVITT
• 金额: $ 38.19万
• 依托单位: SYNAGEVA BIOPHARMA CORPORATION
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6834199
• 关键词: artificial chromosomes; biotherapeutic agent; chickens; drug design /synthesis /production; egg /ovum; gene expression; genetic regulatory element; genetically modified animals; messenger RNA; microinjections; monoclonal antibody; ovalbumin; ovomucoid; reporter genes; transfection; transfection /expression vector

DESCRIPTION (provided by applicant): With a daily production of 400 to 2500 milligrams of protein per egg, the chicken ovomucoid and ovalbumin gene loci have the potential to synthesize large amounts of biopharmaceutical proteins in transgenic hens. This phase II SBIR project will test the feasibility of using large oviduct protein genomic locus expression constructs, created and tested in phase I, to drive efficient expression of biopharmaceutical proteins into egg white of transgenic hens. The bacterial artificial chromosome (BAC) constructs to be used contain the complete ovomucoid or ovalbumin genomic locus with IRES-transgene cassettes inserted into the 3' UTR of the mRNA transcript The transgenes contained in these constructs are a human monoclonal antibody and an immunoglobulin fusion protein. Transgenic birds will be generated by microinjection of early embryos followed by transfer of the ovum to the oviduct of recipient hens. Transgenic protein from Go, G1 and G2 birds will be assessed for expression levels, and bioactivity.

描述（由申请人提供）：鸡卵类粘蛋白和卵清蛋白基因座具有在转基因母鸡中合成大量生物药物蛋白的潜力，每个鸡蛋每天产生400至2500毫克蛋白质。该二期SBIR项目将测试使用在一期中创建和测试的大输卵管蛋白基因组位点表达构建体来驱动生物药物蛋白在转基因母鸡的白色中有效表达的可行性。待使用的细菌人工染色体（BAC）构建体含有完整的卵类粘蛋白或卵清蛋白基因组基因座，其中IRES-转基因盒插入mRNA转录物的3' UTR中。这些构建体中含有的转基因是人单克隆抗体和免疫球蛋白融合蛋白。转基因鸡将通过显微注射早期胚胎，然后将卵子转移到受体母鸡的输卵管中来产生。将评估来自G 0、G1和G2禽类的转基因蛋白的表达水平和生物活性。