Recent advances in half-life extension strategies for therapeutic peptides and proteins

• Published in: Current pharmaceutical design
• Main Authors: Tan, Huanbo, Su, Wencheng, Zhang, Wenyu, Wang, Pengju, Sattler, Michael, Zou, Peijian
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2018
• Subjects: FcRn; Peptides and proteins; half-life extension strategies; renal clearance; long-acting
• ISSN: 1873-4286
• DOI: 10.2174/1381612825666190206105232

Peptides and proteins are two classes of molecules with attractive possibilities for therapeutic applications. However, the bottleneck for the therapeutic application of many peptides and proteins is their short half-lives in vivo, typically just a few minutes to hours. Half-life extension strategies have been extensively studied and many of them have been proved to be effective in generation of long-acting therapeutics with improved pharmacokinetic and pharmacodynamic properties. In this review, we summarize the recent advances in half-life extension strategies, illustrate their potential applications and give some examples, highlighting the strategies that have been used in approved drugs and for drugs in clinical trials. Meanwhile, several novel strategies that are still in the process of discovery or in a preclinical stage are also introduced. In these strategies, the two most frequently used half-life extension methods are to reduce the rate of renal clearance or to exploit the recycling mechanism of FcRn by binding to the albumin or IgG-Fc. Here, we discuss half-life extension strategies of recombinant therapeutic protein via genetic fusion, rather than chemical conjugation such as PEGylation. With the rapid development of genetic engineering and protein engineering, novel strategies for half-life extension have been emerging consistently. Some of them will be evaluated in clinical trials and may be viable alternatives to current strategies for making next-generation biodrugs.