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- Title
Bioorthogonal Engineered Virus-Like Nanoparticles for Efficient Gene Therapy.
- Authors
Bao, Chun-Jie; Duan, Jia-Lun; Xie, Ying; Feng, Xin-Ping; Cui, Wei; Chen, Song-Yue; Li, Pei-Shan; Liu, Yi-Xuan; Wang, Jin-Ling; Wang, Gui-Ling; Lu, Wan-Liang
- Abstract
Highlights: A virus-like nanoparticle (reBiosome) was developed via site-specific codon mutation for displaying unnatural amino acid (Azi) on virus envelope protein at a rational site, followed by conjugating weak acid-responsive polyethylene glycol polymer on Azi via bioorthogonal chemistry. The reBiosome exhibited reduced virus-like immunogenicity, prolonged blood circulation and enhanced delivery to weakly acidic disease foci. The reBiosome enabled efficient delivery of gene editing and gene silencing system, demonstrating remarkable therapeutic efficacy in breast cancer and arthritis, respectively. 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.
- Subjects
GENE therapy; GENOME editing; VESICULAR stomatitis; GENE silencing; POLYETHYLENE glycol; GENETIC code; VIRAL envelope proteins
- Publication
Nano-Micro Letters, 2023, Vol 15, Issue 1, p1
- ISSN
2311-6706
- Publication type
Article
- DOI
10.1007/s40820-023-01153-y