한빛사논문
Seoungkyun Kim, Dong Hee Kim, Jinhwan Cho, Jaeyun Kim,* and Inchan Kwon*
S. Kim, J. Cho, I. Kwon
School of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea
I. Kwon
Research Center for Innovative Energy and Carbon Optimized Synthesis for Chemicals (Inn-ECOSysChem), Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea
D. H. Kim, J. Kim
School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
J. Kim
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
S.K. and D.H.K. contribute equally to this work.
CORRESPONDING AUTHORS: Jaeyun Kim, Inchan Kwon
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 half-life 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.
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