Granulocyte colony-stimulating factor (GCSF) fused with Fc Domain produced from E. coli is less effective than Polyethylene Glycol-conjugated GCSF

Abstract Human granulocyte colony-stimulating factor (GCSF) is a well-known cytokine for neutropenia treatment. However, daily injections are required due to the short circulating half-life of the protein. To overcome this bottleneck, we fused GCSF with the Fc domain of IgG1 at the C terminus (GCSF-...

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Autores principales:	Bich Hang Do, Hyo Jeong Kang, Jung-A Song, Minh Tan Nguyen, Sangsu Park, Jiwon Yoo, Anh Ngoc Nguyen, Grace G. Kwon, Jaepyeong Jang, Mihee Jang, Sunju Lee, Seoungjun So, Seongrak Sim, Kyung Jin Lee, Mark J. Osborn, Han Choe
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Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/498d10aac9f44f84bf57cdd46d5d4363
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spelling	oai:doaj.org-article:498d10aac9f44f84bf57cdd46d5d43632021-12-02T16:06:51ZGranulocyte colony-stimulating factor (GCSF) fused with Fc Domain produced from E. coli is less effective than Polyethylene Glycol-conjugated GCSF10.1038/s41598-017-06726-72045-2322https://doaj.org/article/498d10aac9f44f84bf57cdd46d5d43632017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06726-7https://doaj.org/toc/2045-2322Abstract Human granulocyte colony-stimulating factor (GCSF) is a well-known cytokine for neutropenia treatment. However, daily injections are required due to the short circulating half-life of the protein. To overcome this bottleneck, we fused GCSF with the Fc domain of IgG1 at the C terminus (GCSF-Fc) and with the maltose binding protein (MBP) tag at the N-terminus and expressed it as a soluble protein in the cytoplasm of E. coli. We also conjugated PEG aldehyde to GCSF to make PEG-GCSF. The bioactivities of GCSF-Fc and PEG-GCSF were similar to native GCSF using the mouse M-NFS-60 myelogenous leukemia cell line. The EC50 dose-response curves for GCSF, GCSF-Fc and PEG-GCSF were 37 ± 12 pM, 75 ± 13.5 pM and 46 ± 5.5 pM, respectively. When the proteins were injected into neutropenic rats, the group injected with PEG-GCSF showed the highest and fastest recovery of neutrophils, followed by GCSF-Fc and GCSF. ELISA assay revealed the PEG-GCSF had the longest plasma circulation (>72 h), followed by GCSF-Fc (>48 h) and GCSF (~24 h), which is consistent with the in vivo activities of the proteins. In summary, the GCSF-Fc purified from E. coli was not as efficient as PEG-GCSF in treating neutropenic rats.Bich Hang DoHyo Jeong KangJung-A SongMinh Tan NguyenSangsu ParkJiwon YooAnh Ngoc NguyenGrace G. KwonJaepyeong JangMihee JangSunju LeeSeoungjun SoSeongrak SimKyung Jin LeeMark J. OsbornHan ChoeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bich Hang Do Hyo Jeong Kang Jung-A Song Minh Tan Nguyen Sangsu Park Jiwon Yoo Anh Ngoc Nguyen Grace G. Kwon Jaepyeong Jang Mihee Jang Sunju Lee Seoungjun So Seongrak Sim Kyung Jin Lee Mark J. Osborn Han Choe Granulocyte colony-stimulating factor (GCSF) fused with Fc Domain produced from E. coli is less effective than Polyethylene Glycol-conjugated GCSF
description	Abstract Human granulocyte colony-stimulating factor (GCSF) is a well-known cytokine for neutropenia treatment. However, daily injections are required due to the short circulating half-life of the protein. To overcome this bottleneck, we fused GCSF with the Fc domain of IgG1 at the C terminus (GCSF-Fc) and with the maltose binding protein (MBP) tag at the N-terminus and expressed it as a soluble protein in the cytoplasm of E. coli. We also conjugated PEG aldehyde to GCSF to make PEG-GCSF. The bioactivities of GCSF-Fc and PEG-GCSF were similar to native GCSF using the mouse M-NFS-60 myelogenous leukemia cell line. The EC50 dose-response curves for GCSF, GCSF-Fc and PEG-GCSF were 37 ± 12 pM, 75 ± 13.5 pM and 46 ± 5.5 pM, respectively. When the proteins were injected into neutropenic rats, the group injected with PEG-GCSF showed the highest and fastest recovery of neutrophils, followed by GCSF-Fc and GCSF. ELISA assay revealed the PEG-GCSF had the longest plasma circulation (>72 h), followed by GCSF-Fc (>48 h) and GCSF (~24 h), which is consistent with the in vivo activities of the proteins. In summary, the GCSF-Fc purified from E. coli was not as efficient as PEG-GCSF in treating neutropenic rats.
format	article
author	Bich Hang Do Hyo Jeong Kang Jung-A Song Minh Tan Nguyen Sangsu Park Jiwon Yoo Anh Ngoc Nguyen Grace G. Kwon Jaepyeong Jang Mihee Jang Sunju Lee Seoungjun So Seongrak Sim Kyung Jin Lee Mark J. Osborn Han Choe
author_facet	Bich Hang Do Hyo Jeong Kang Jung-A Song Minh Tan Nguyen Sangsu Park Jiwon Yoo Anh Ngoc Nguyen Grace G. Kwon Jaepyeong Jang Mihee Jang Sunju Lee Seoungjun So Seongrak Sim Kyung Jin Lee Mark J. Osborn Han Choe
author_sort	Bich Hang Do
title	Granulocyte colony-stimulating factor (GCSF) fused with Fc Domain produced from E. coli is less effective than Polyethylene Glycol-conjugated GCSF
title_short	Granulocyte colony-stimulating factor (GCSF) fused with Fc Domain produced from E. coli is less effective than Polyethylene Glycol-conjugated GCSF
title_full	Granulocyte colony-stimulating factor (GCSF) fused with Fc Domain produced from E. coli is less effective than Polyethylene Glycol-conjugated GCSF
title_fullStr	Granulocyte colony-stimulating factor (GCSF) fused with Fc Domain produced from E. coli is less effective than Polyethylene Glycol-conjugated GCSF
title_full_unstemmed	Granulocyte colony-stimulating factor (GCSF) fused with Fc Domain produced from E. coli is less effective than Polyethylene Glycol-conjugated GCSF
title_sort	granulocyte colony-stimulating factor (gcsf) fused with fc domain produced from e. coli is less effective than polyethylene glycol-conjugated gcsf
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/498d10aac9f44f84bf57cdd46d5d4363
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Granulocyte colony-stimulating factor (GCSF) fused with Fc Domain produced from E. coli is less effective than Polyethylene Glycol-conjugated GCSF

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