کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4752465 | 1416150 | 2017 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Single chain Fc-dimer-human growth hormone fusion protein for improved drug delivery
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
مهندسی شیمی
بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 117, February 2017, Pages 24-31
Journal: Biomaterials - Volume 117, February 2017, Pages 24-31
نویسندگان
Li Zhou, Hsuan-Yao Wang, Shanshan Tong, Curtis T. Okamoto, Wei-Chiang Shen, Jennica L. Zaro,