The proper strategy to compress and protect plasmid DNA in the Pluronic L64-electropulse system for enhanced intramuscular gene delivery

作     者：Yutong He Yili Liu Zhe Sun Fei Han James Zhenggui Tang Rong Gao Gang Wang 

作者机构：National Engineering Research Center for Biomaterials Key Laboratory for Bio-Resource and Eco-Environment of Ministry EducationCollege of Life ScienceSichuan UniversityNo.29Wangjiang RoadChengduSichuan 610064P.R.China Research Institute in Healthcare ScienceFaculty of Science and EngineeringSchool of PharmacyUniversity of WolverhamptonWolverhampton WV11SBUK 

出 版 物：《Regenerative Biomaterials》 (再生生物材料（英文版）)

年 卷 期：2019年第6卷第5期

页      面：289-298页

核心收录：

学科分类：0831[工学-生物医学工程（可授工学、理学、医学学位）] 1002[医学-临床医学] 0805[工学-材料科学与工程（可授工学、理学学位）] 100214[医学-肿瘤学] 10[医学] 

基　　金：the National Natural Science Foundation of China(no.31370972) the 111 Project(no.B16033) the National Key Research and Development Program of China(2017YFB0702600,2017YFB0702603)。 

主　　题：muscle-based gene delivery gene therapy EGCG PEI Pluronic L64-electropulse 

摘      要：Intramuscular expression of functional proteins is a promising strategy for therapeutic purposes.Previously,we developed an intramuscular gene delivery method by combining Pluronic L64 and optimized electropulse,which is among the most efficient methods to date.However,plasmid DNAs(pDNAs)in this method were not compressed,making them unstable and inefficient in vivo.We considered that a proper compression of pDNAs by an appropriate material should facilitate gene expression in this L64-electropulse system.Here,we reported our finding of such a material,Epigallocatechin gallate(EGCG),a natural compound in green teas,which could compress and protect pDNAs and significantly increase intramuscular gene expression in the L64-electropulse system.Meanwhile,we found that polyethylenimine(PEI)could also slightly improve exogenous gene expression in the optimal procedure.By analysing the characteristic differences between EGCG and PEI,we concluded that negatively charged materials with strong affinity to nucleic acids and/or other properties suitable for gene delivery,such as EGCG,are better alternatives than cationic materials(like PEI)for muscle-based gene delivery.The results revealed that a critical principle for material/pDNA complex benefitting intramuscular gene delivery/expression is to keep the complex negatively charged.This proof-of-concept study displays the breakthrough in compressing pDNAs and provides a principle and strategy to develop more efficient intramuscular gene delivery systems for therapeutic applications.