Traceless photodegradable polymer cocoons for universal protein delivery and light-controlled gene editing  

作　　者：Huaibin Yu Meron Tsegay Kifle Lili Chen Feihong Xiong Yan Zhang Shangbang Gao Wei Hou Shuliang Chen Weining Zhao Yuzhou Wu 

机构地区：[1]Hubei Engineering Research Center for Biomaterials and Medical Protective Materials,Hubei Key Laboratory of Bioinorganic Chemistry&Materia Medica,Key Laboratory of Material Chemistry for Energy Conversion and Storage,Ministry of Education,School of Chemistry and Chemical Engineering,Huazhong University of Science and Technology(HUST),Wuhan,430074,China [2]Zhengzhou Research Institute,Harbin Institute of Technology,Zhengzhou,450000,China [3]College of Life Science and Technology,Huazhong University of Science and Technology(HUST),Wuhan,430074,China [4]Institute of Medical Virology,School of Basic Medical Sciences,Wuhan University,Wuhan,430071,China [5]College of Pharmacy,Shenzhen Technology University,Shenzhen,518118,China

出　　处：《Science China Chemistry》2024年第2期664-676,共13页中国科学（化学英文版）

基　　金：supported by the National Key R&D Program of China (2018YFA0903500);the Max-Planck Partner Group;the National Natural Science Foundation of China (22077042);the National Key Research and Development Program of China (2022YFA1206001 to S.G.)。

摘　　要：Polymer conjugation was found highly valuable in clinic to improve the bioavailability of protein therapeutics.However,it is still a tremendous challenge to achieve a complete release of original proteins from the conjugated hybrid under external stimulus to recover active proteins in the targeted tissue.Herein,we report a general light-controlled protein delivery methodology by weaving a photodegradable polymer cocoon around proteins,which could reliably protect them from degradation in the dark while efficiently releasing them under illumination without any residual atoms.The surface charge of the polymer shell is easily tunable to facilitate efficient cell uptake.The versatility of this strategy is demonstrated by the delivery of the Cas9/sg RNA complex that realized light-controlled gene editing both in vitro and in vivo,and such repertoire is of particular value in regard to minimizing the off-target toxicity of CRISPR-Cas9-based gene therapy.

关 键 词：photodegradable polymer-protein conjugate protein delivery light control gene editing 

分 类 号：TQ931[化学工程]