Journal
BIOMATERIALS
Volume 117, Issue -, Pages 24-31Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2016.11.051
Keywords
Fc fusion; Single chain Fc; Protein delivery; Human growth hormone; Pharmacokinetics; Pharmacodynamics
Funding
- Jiangsu Government Scholarship for Overseas Studies, Jiangsu Provincial Department of Education
- University of Southern California School of Pharmacy
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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 FcyR-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. (C) 2016 Elsevier Ltd. All rights reserved.
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