Bioorthogonal Engineered Virus-Like Nanoparticles for Efficient Gene Therapy

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.