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

Abstract

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. The current study shows that 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 is introduced into urate oxidase (UOX), a therapeutic protein for gout, to generate UOX variants with varying net charges. When a positively-charged injectable hydrogel is used, both the in vitro release rate and in vivo serum half-life of UOX are correlated with the net negative charge. This modified delivery approach results in a serum halflife of over 106 h for the UOX variant, which is substantially longer than that of free UOX (3.3 h). Hence, charge booster tags can be used as a systematic strategy for controlling the release of therapeutic proteins.

AlbuCatcher for Long-Acting Therapeutics

“…The enzyme activities of Uox species (Uox-WT, Uox-ST, and Uox-HSA) were measured by the uric acid degradation assay as described previously with slight modifications. , The reaction was carried out at 37 °C, where 60 nM Uox species was incubated with 200 μM of uric acid in 200 μL of PBS (pH 7.4). The degradation of uric acid was then monitored by measuring the change in the optical density at 293 nm.…”