Open AccessStructural and functional characterization of recombinant human growth hormone isolated from transgenic pig milk
Author(s) -
SoYoung Lee,
Joo-Hee Han,
Eun-Kyeong Lee,
Young Kyu Kim,
Seo-Ah Hwang,
Sung-Hyun Lee,
Maria Kim,
Gye Yoon Cho,
Jaewon Hwang,
Sujin Kim,
JiHyock Yoo,
SeongKeun Cho,
KyungJu Lee,
Weon-Ki Cho
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0236788
Subject(s) - transgene , recombinant dna , somatropin , genetically modified mouse , toxicity , genetically modified organism , biology , growth hormone , chemistry , biochemistry , hormone , medicine , gene
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.