Oviduct locus BACs for expression of bio-therapeutics

描述（由申请人提供）：每个鸡蛋每天生产400至2500毫克蛋白质，鸡类卵粘液和卵清蛋白基因位点具有在转基因母鸡中合成大量生物制药蛋白质的潜力。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的可行性，以推动生物制药蛋白在转基因母鸡的蛋清中高效表达。所使用的细菌人工染色体（BAC）构建物包含完整的卵泡样蛋白或卵清蛋白基因组位点，并在mRNA转录物的3' UTR中插入ires -转基因磁带。这些构建物中包含的转基因是人单克隆抗体和免疫球蛋白融合蛋白。转基因鸡将通过对早期胚胎进行显微注射，然后将卵子移植到受体母鸡的输卵管中来产生。将评估Go、G1和G2鸟的转基因蛋白的表达水平和生物活性。

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.