2. Academic Validation
  3. Bioorthogonal Engineered Virus-Like Nanoparticles for Efficient Gene Therapy

Bioorthogonal Engineered Virus-Like Nanoparticles for Efficient Gene Therapy

  • Nanomicro Lett. 2023 Aug 12;15(1):197. doi: 10.1007/s40820-023-01153-y.
Chun-Jie Bao # 1 2 3,  Jia-Lun Duan # 1 2,  Ying Xie # 1,  Xin-Ping Feng 4,  Wei Cui 4,  Song-Yue Chen 1,  Pei-Shan Li 1,  Yi-Xuan Liu 1,  Jin-Ling Wang 1,  Gui-Ling Wang 1,  Wan-Liang Lu 5
Affiliations

Affiliations

  • 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.
  • 5 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. luwl@bjmu.edu.cn.
  • # Contributed equally.
PMID: 37572220 DOI: 10.1007/s40820-023-01153-y
Abstract

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.

Keywords

Bioorthogonal chemistry; Gene therapy; Recombinant biosome; Site-specific codon mutation; Virus-like nanoparticle.

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