Bioorthogonal Engineered Virus‑Like Nanoparticles for Efficient Gene Therapy  

作　　者：Chun‑Jie Bao Jia‑Lun Duan Ying Xie Xin‑Ping Feng Wei Cui Song‑Yue Chen Pei‑Shan Li Yi‑Xuan Liu Jin‑Ling Wang Gui‑Ling Wang Wan‑Liang Lu 

机构地区：[1]State Key Laboratory of Natural and Biomimetic Drugs,Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems,and School of Pharmaceutical Sciences,Peking University,Beijing 100191,People’s Republic of China [2]Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization,Nanjing University of Chinese Medicine,Nanjing 210023,People’s Republic of China [3]School of Medicine&Holistic Integrative Medicine,Nanjing University of Chinese Medicine,Nanjing 210023,People’s Republic of China [4]School of Chemical Sciences,University of Chinese Academy of Sciences,Beijing 100049,People’s Republic of China

出　　处：《Nano-Micro Letters》2023年第11期119-135,共17页纳微快报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant No.81874303 and No.82173752 W.L.Lu).

摘　　要：Gene therapy offers potentially transformative strategies for major human diseases.However,one of the key challenges in gene therapy is developing an effective strategy that could deliver genes into the specific tissue.Here,we report a novel virus-like nanoparticle,the bioorthgonal engineered viruslike recombinant biosome(reBiosome),for efficient gene therapies of cancer and inflammatory diseases.The mutant virus-like biosome(mBiosome)is first prepared by site-specific codon mutation for displaying 4-azido-L-phenylalanine on vesicular stomatitis virus glycoprotein of eBiosome at a rational site,and the reBiosome is then prepared by clicking weak acid-responsive hydrophilic polymer onto the mBiosome via bioorthogonal chemistry.The results show that the reBiosome exhibits reduced virus-like immunogenicity,prolonged blood circulation time and enhanced gene delivery efficiency to weakly acidic foci(like tumor and arthritic tissue).Furthermore,reBiosome demonstrates robust therapeutic efficacy in breast cancer and arthritis by delivering gene editing and silencing systems,respectively.In conclusion,this study develops a universal,safe and efficient platform for gene therapies for cancer and inflammatory diseases.

关 键 词：Virus-like nanoparticle Site-specific codon mutation Recombinant biosome Bioorthogonal chemistry Gene therapy 

分 类 号：TB383.1[一般工业技术—材料科学与工程] R450[医药卫生—治疗学]