Charge Booster Tags for Controlled Release of Therapeutics from a Therapeutic Carrier

摘要

Injectable hydrogels are promising delivery vehicles for the sustained releaseof therapeutic proteins. Electrostatic interactions between proteins andhydrogels often increase affinity to decelerate protein release. However,this approach is not suitable for weakly charged proteins. The current studyshows that the genetic fusion of a highly charged protein segment (chargebooster tag) with proteins can control their interactions with injectable gels.A positive or negative charge booster tag is introduced into urate oxidase(UOX), a therapeutic protein for gout, to generate UOX variants with varyingnet charges. When a positively-charged injectable hydrogel is used, both thein vitro release rate and in vivo serum half-life of UOX are correlated with thenet negative charge. This modified delivery approach results in a serum halflifeof over 106 h for the UOX variant, which is substantially longer than thatof free UOX (3.3 h). Hence, charge booster tags can be used as a systematicstrategy for controlling the release of therapeutic proteins.