Improving gene transfection efficiency of highly branched poly(β-amino ester)s through the in-situ conversion of inactive terminal groups

作     者：Zhili Li Qijun Wo Dongdong Huang Dezhong Zhou Lei Guo Yeqing Mao Zhili Li;Qijun Wo;Dongdong Huang;Dezhong Zhou;Lei Guo;Yeqing Mao

作者机构：Department of UrologyThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310000China School of Chemical Engineering and TechnologyXi’an Jiaotong UniversityXi’an 710049China Urology&Nephrology CenterDepartment of UrologyZhejiang Provincial People’s Hospital(Affiliated People’s Hospital)Hangzhou Medical CollegeHangzhou 310014China Key Laboratory of Endocrine Gland Diseases of Zhejiang ProvinceHangzhou 310014China Pooling Institute of Translational MedicineHangzhou 311100China 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2024年第35卷第8期

页      面：304-308页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 

基　　金：funded by the National Natural Science Foundation of China(NSFC,No.51903202) the Key R&D Program of Shaanxi Province(No.2020GXLH-Y-016) the Natural Science Foundation of Shaanxi Province(No.2020JM-055) the Fundamental Re-search Funds for the Central Universities(No.xtr042019020) the Young Talents Support Plan of Xi’an Jiaotong University(No.HG6J002) 

主　　题：Gene therapy Gene delivery vector Highly branched poly(β-amino ester)s Terminal groups Epithelial cells 

摘      要：Highly branched poly(β-amino ester)s(HPAEs)have emerged as a safe and efficient type of non-viral gene delivery ***,the presence of inactive terminal secondary amine groups compromises their gene transfection *** this study,HPAEs with similar topological structures and chemical compositions but varying numbers of terminal secondary 4-amino-1-butanol(S4)and secondary/tertiary 3-morpholinopropylamine(MPA)groups were *** results demonstrate that an increased number of secondary/tertiary MPA groups in-situ significantly enhances the DNA binding capability of HPAEs,leading to the formation of smaller HPAE/DNA polyplexes with higher zeta potential,ultimately resulting in superior gene transfection efficiency in bladder epithelial *** study establishes a sim-ple yet effective strategy to maximize the gene transfection potency of HPAEs by converting the inactive terminal groups in-situ without the need for complex modifications to their topological structure and chemical composition.