Bioorthogonal Engineered Virus-Like Nanoparticles for Efficient Gene Therapy

被引：9

作者：

Bao, Chun-Jie ^{[1
,2
,3
,4
]}

Duan, Jia-Lun ^{[1
,2
,3
]}

Xie, Ying ^{[1
,2
]}

Feng, Xin-Ping ^{[5
]}

Cui, Wei ^{[5
]}

Chen, Song-Yue ^{[1
,2
]}

Li, Pei-Shan ^{[1
,2
]}

Liu, Yi-Xuan ^{[1
,2
]}

Wang, Jin-Ling ^{[1
,2
]}

Wang, Gui-Ling ^{[1
,2
]}

Lu, Wan-Liang ^{[1
,2
]}

机构：

[1] Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing Key Lab Mol Pharmaceut & Drug Delivery Sys, Beijing 100191, Peoples R China

[2] Peking Univ, Sch Pharmaceut Sci, Beijing 100191, Peoples R China

[3] Nanjing Univ Chinese Med, Jiangsu Collaborat Innovat Ctr Chinese Med Resourc, Nanjing 210023, Peoples R China

[4] Nanjing Univ Chinese Med, Sch Med & Holist Integrat Med, Nanjing 210023, Peoples R China

[5] Univ Chinese Acad Sci, Sch Chem Sci, Beijing 100049, Peoples R China

来源：

NANO-MICRO LETTERS | 2023年 / 15卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Virus-like nanoparticle; Site-specific codon mutation; Recombinant biosome; Bioorthogonal chemistry; Gene therapy; PROTEIN; PARTICLES; RECEPTOR; ALPHA; RNA;

D O I：

10.1007/s40820-023-01153-y

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

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 virus-like 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.

引用

页数：17

共 48 条

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