Structural and functional characterization of recombinant human growth hormone isolated from transgenic pig milk.
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 tech...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0236788 |
| _version_ | 1818404218650755072 |
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| author | So-Young Lee Joo-Hee Han Eun-Kyeong Lee Young Kyu Kim Seo-Ah Hwang Sung-Hyun Lee Maria Kim Gye Yoon Cho Jae-Ha Hwang Su-Jin Kim Jae-Gyu Yoo Seong-Keun Cho Kyung-Ju Lee Weon-Ki Cho |
| author_facet | So-Young Lee Joo-Hee Han Eun-Kyeong Lee Young Kyu Kim Seo-Ah Hwang Sung-Hyun Lee Maria Kim Gye Yoon Cho Jae-Ha Hwang Su-Jin Kim Jae-Gyu Yoo Seong-Keun Cho Kyung-Ju Lee Weon-Ki Cho |
| author_sort | So-Young Lee |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T08:36:40Z |
| format | Article |
| id | doaj.art-8ca3256c9b834ae1a97798ca26fdbff2 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T08:36:40Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8ca3256c9b834ae1a97798ca26fdbff22022-12-21T23:09:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01157e023678810.1371/journal.pone.0236788Structural and functional characterization of recombinant human growth hormone isolated from transgenic pig milk.So-Young LeeJoo-Hee HanEun-Kyeong LeeYoung Kyu KimSeo-Ah HwangSung-Hyun LeeMaria KimGye Yoon ChoJae-Ha HwangSu-Jin KimJae-Gyu YooSeong-Keun ChoKyung-Ju LeeWeon-Ki ChoThis 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.https://doi.org/10.1371/journal.pone.0236788 |
| spellingShingle | So-Young Lee Joo-Hee Han Eun-Kyeong Lee Young Kyu Kim Seo-Ah Hwang Sung-Hyun Lee Maria Kim Gye Yoon Cho Jae-Ha Hwang Su-Jin Kim Jae-Gyu Yoo Seong-Keun Cho Kyung-Ju Lee Weon-Ki Cho Structural and functional characterization of recombinant human growth hormone isolated from transgenic pig milk. PLoS ONE |
| title | Structural and functional characterization of recombinant human growth hormone isolated from transgenic pig milk. |
| title_full | Structural and functional characterization of recombinant human growth hormone isolated from transgenic pig milk. |
| title_fullStr | Structural and functional characterization of recombinant human growth hormone isolated from transgenic pig milk. |
| title_full_unstemmed | Structural and functional characterization of recombinant human growth hormone isolated from transgenic pig milk. |
| title_short | Structural and functional characterization of recombinant human growth hormone isolated from transgenic pig milk. |
| title_sort | structural and functional characterization of recombinant human growth hormone isolated from transgenic pig milk |
| url | https://doi.org/10.1371/journal.pone.0236788 |
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