Suppr超能文献

从转基因猪乳中分离得到的重组人生长激素的结构与功能表征。

Structural and functional characterization of recombinant human growth hormone isolated from transgenic pig milk.

机构信息

CHO-A Biotechnology Research Institute, CHO-A Pharmaceutical Company, Yeoju-si, Gyeonggi-do, Korea.

Department of Animal Science, College of Natural Resources and Life Science, Pusan National University, Miryang-si, Gyeongsangnam-do, Korea.

出版信息

PLoS One. 2020 Jul 31;15(7):e0236788. doi: 10.1371/journal.pone.0236788. eCollection 2020.

Abstract

This study aimed to establish and reproduce transgenic pigs expressing human growth hormone (hGH) in their milk. We also aimed to purify hGH from the milk, to characterize the purified protein, and to assess the potential of our model for mass production of therapeutic proteins using transgenic techniques. Using ~15.5 L transgenic pig milk, we obtained proteins with ≥ 99% purity after three pre-treatments and five column chromatography steps. To confirm the biosimilarity of our milk-derived purified recombinant hGH (CGH942) with commercially available somatropin (Genotropin), we performed spectroscopy, structural, and biological analyses. We observed no difference between the purified protein and Genotropin samples. Furthermore, rat models were used to assess growth promotion potential. Our results indicate that CGH942 promotes growth, by increasing bone development and body weight. Toxicity assessments revealed no abnormal findings after 4 weeks of continuous administration and 2 weeks of recovery. The no-observed-adverse-effect level for both males and females was determined to be 0.6 mg/kg/day. Thus, no toxicological differences were observed between commercially available somatropin and CGH942 obtained from transgenic pig milk. In conclusion, we describe a transgenic technique using pigs, providing a new platform to produce human therapeutic proteins.

摘要

本研究旨在建立和复制在其乳汁中表达人生长激素(hGH)的转基因猪。我们还旨在从乳汁中纯化 hGH,对纯化的蛋白进行表征,并评估我们使用转基因技术大规模生产治疗性蛋白的模型的潜力。使用约 15.5 升转基因猪乳,我们在经过三次预处理和五次柱层析步骤后,获得了纯度≥99%的蛋白。为了确认我们从乳汁中纯化的重组 hGH(CGH942)与市售生长激素(Genotropin)的生物相似性,我们进行了光谱学、结构和生物学分析。我们观察到纯化蛋白与 Genotropin 样品之间没有差异。此外,还使用大鼠模型评估了促生长潜力。我们的结果表明,CGH942 通过增加骨发育和体重来促进生长。毒性评估显示,连续给药 4 周和恢复 2 周后无异常发现。雄性和雌性的无观察到不良效应水平均确定为 0.6 毫克/千克/天。因此,在商业可得的生长激素和从转基因猪乳中获得的 CGH942 之间未观察到毒理学差异。总之,我们描述了一种使用猪的转基因技术,为生产人类治疗性蛋白提供了一个新的平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e950/7394428/135c5f71f0b1/pone.0236788.g001.jpg

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验