Nano-Micro Letters, Volume. 15, Issue 1, 197(2023)

Bioorthogonal Engineered Virus-Like Nanoparticles for Efficient Gene Therapy

Chun-Jie Bao1...2,3,†, Jia-Lun Duan1,2,†, Ying Xie1,†, Xin-Ping Feng4, Wei Cui4, Song-Yue Chen1, Pei-Shan Li1, Yi-Xuan Liu1, Jin-Ling Wang1, Gui-Ling Wang1 and Wan-Liang Lu1,* |Show fewer author(s)
Author Affiliations
  • 1State 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
  • 2Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, People’s Republic of China
  • 3School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, People’s Republic of China
  • 4School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of China
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    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.

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    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. Bioorthogonal Engineered Virus-Like Nanoparticles for Efficient Gene Therapy[J]. Nano-Micro Letters, 2023, 15(1): 197

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    Paper Information

    Category: Research Articles

    Received: Apr. 10, 2023

    Accepted: Jun. 20, 2023

    Published Online: Dec. 15, 2023

    The Author Email: Lu Wan-Liang (luwl@bjmu.edu.cn)

    DOI:10.1007/s40820-023-01153-y

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