Transgenic chickens for protein production

用于生产蛋白质的转基因鸡

基本信息

批准号：
6789031
负责人：
Robert J Etches
金额：
$ 11.42万
依托单位：
ORIGEN THERAPEUTICS
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-06-10 至 2004-12-09
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Chimeric chickens can be produced by injecting embryonic stem (ES) cells into recipient embryos in newly laid, unincubated eggs. The embryonic stem cells contribute to all somatic tissues and sporadically to the germline. The ratio of embryonic stem cell-derived and recipient-derived contributions to the germline can be manipulated by increasing the population of ES cell-derived germ cells. Conversely, the ratio of ES cell derived and recipient derived germ cells can be altered by removing and/or deleting contributions to the germline from the recipient. This application describes technologies to enhance the contribution of ES cell derived germ cells and reduce the contribution of the recipient embryo to the germline. It is anticipated that this shift in the ratio of ES cell-derived to recipient-derived germ cells will produce chimeras that have a larger number of gametes from the embryonic stem cell lineage. If the embryonic cells are carrying transgenes encoding the production of foreign proteins, this technology should provide a robust system for the establishment of founder transgenic chickens that deposit novel proteins in their eggs. The egg is an ideal repository for pharmaceutically important proteins because the egg is a sterile package, each hen lays approximately 300 eggs per year, technology for housing a few or many hens under specific pathogen free conditions is well known, fractionation of proteins in eggs is well understood, and the glycosylation pattern of chickens is similar to that of humans. These attributes make chickens an attractive option for the large-scale production of therapeutic proteins such as monoclonal antibodies.

描述（由申请人提供）：嵌合鸡可以通过将胚胎干（ES）细胞注射到新产的、未孵化的鸡蛋中的受体胚胎中来生产。胚胎干细胞对所有体细胞组织都有贡献，偶尔也对种系有贡献。胚胎干细胞来源和受体来源对种系的贡献比例可以通过增加 ES 细胞来源的生殖细胞数量来控制。相反，ES细胞衍生的生殖细胞和受体衍生的生殖细胞的比率可以通过去除和/或删除受体对种系的贡献来改变。该申请描述了增强ES细胞衍生的生殖细胞的贡献并减少受体胚胎对生殖系的贡献的技术。预计ES细胞衍生的生殖细胞与受体衍生的生殖细胞比例的这种转变将产生具有更多来自胚胎干细胞谱系的配子的嵌合体。如果胚胎细胞携带编码产生外源蛋白质的转基因，那么这项技术应该为建立在鸡蛋中沉积新蛋白质的创始转基因鸡提供一个强大的系统。鸡蛋是药学上重要的蛋白质的理想储存库，因为鸡蛋是无菌包装，每只母鸡每年产下大约 300 个鸡蛋，在特定的无病原体条件下饲养几只或多只母鸡的技术是众所周知的，鸡蛋中蛋白质的分离是众所周知的。很好理解，鸡的糖基化模式与人类相似。这些特性使鸡成为大规模生产单克隆抗体等治疗性蛋白质的有吸引力的选择。