Single chain Fc-dimer-human growth hormone fusion protein for improved drug delivery

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• 作者：Li Zhou^a ; Hsuan-Yao Wang^a ; Shanshan Tong^a ; ^b ; Curtis T. Okamoto^a ; Wei-Chiang Shen^a ; ^{weishen@usc.edu} ; Jennica L. Zaro^a ; ^c ; ^{jZaro@westcoastuniversity.edu}
• 关键词：Fc fusion ; Single chain Fc ; Protein delivery ; Human growth hormone ; Pharmacokinetics ; Pharmacodynamics
• 刊名：Biomaterials
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：117
• 期：Complete
• 页码：24-31
• 全文大小：1389 K
• 卷排序：117

文摘

Fc fusion protein technology has been successfully used to generate long-acting forms of several protein therapeutics. In this study, a novel Fc-based drug carrier, single chain Fc-dimer (sc(Fc)2), was designed to contain two Fc domains recombinantly linked via a flexible linker. Since the Fc dimeric structure is maintained through the flexible linker, the hinge region was omitted to further stabilize it against proteolysis and reduce FcγR-related effector functions. The resultant sc(Fc)2 candidate preserved the neonatal Fc receptor (FcRn) binding. sc(Fc)2-mediated delivery was then evaluated using a therapeutic protein with a short plasma half-life, human growth hormone (hGH), as the protein drug cargo. This novel carrier protein showed a prolonged in vivo half-life and increased hGH-mediated bioactivity compared to the traditional Fc-based drug carrier. sc(Fc)2 technology has the potential to greatly advance and expand the use of Fc-technology for improving the pharmacokinetics and bioactivity of protein therapeutics.