Gwangju Institute of Science and Technology (GIST),
Keywords: therapeutic protein, controlled release, injectable gels
Summary:Injectable hydrogels are promising delivery vehicles for the sustained release of therapeutic proteins. Electrostatic interactions between proteins and hydrogels often increase affinity to decelerate protein release. However, this approach is not suitable for weakly charged proteins. Therefore, we investigated whether the genetic fusion of a highly charged protein segment (charge booster tag) with proteins can control their interactions with injectable gels. A positive or negative charge booster tag was introduced into urate oxidase (UOX), a therapeutic protein for gout, to generate UOX variants with varying net charges. When a positively-charged injectable hydrogel was used, both the in vitro release rate and in vivo serum half-life of UOX were correlated with the net negative charge. This modified delivery approach resulted in a serum half-life of over 100 h for the UOX variant, which was substantially longer than that of free UOX. Hence, we believe charge booster tags can be used as a systematic strategy for controlling the release of therapeutic proteins.