Site-Specific Albumination for the Enhanced Serum Half-Life In Vivo

I. Kwon
Gwangju Institute of Science and Technology,

Keywords: albumination, serum half-life, PEG


Polyethylene glycol (PEG) has been widely used as a serum half-life extender of therapeutic proteins. However, due to immune responses and low degradability of PEG, developing serum half-life extenders alternative to PEG is required. Human serum albumin (HSA) has several beneficial features as a serum half-life extender, including a very long serum half-life, good degradability, and low immune responses. In order to further evaluate the efficacy of HSA, we compared the extent of serum half-life extension of a target protein, superfolder green fluorescent protein (sfGFP), upon HSA conjugation with PEG conjugation side-by-side. Combination of site-specific incorporation of p-azido-L-phenylalanine into sfGFP and copper-free click chemistry achieved the site-specific conjugation of a single HSA or PEG molecule to sfGFP. These sfGFP conjugates exhibited the fluorescence comparable to or even greater than that of sfGFP-WT. In mice, HSA-conjugation to sfGFP extended the serum half-life 9.0 times compared to that of unmodified sfGFP, which is comparable to those of PEG-conjugated sfGFPs. These results clearly demonstrated that HSA was as effective as PEG in extending the serum half-life of a target protein. Therefore, with the additional favorable features, HSA is a good serum half-life extender of a (therapeutic) protein as an alternative to PEG.