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 halflives
in vivo, typically just a few minutes to hours. Half-life extension strategies have been extensively studied
and many of them have been proven to be effective in the 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 at a preclinical stage are also introduced. In these strategies, the two most frequently
used half-life extension methods are the reduction in the rate of renal clearance or the exploitation of 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 emerged consistently. Some of these will be evaluated in clinical trials and may become viable alternatives
to current strategies for making next-generation biodrugs.
Keywords: Peptides and proteins, half-life extension strategies, long-acting, renal clearance, FcRn, pharmacodynamic properties.
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