The in vivo fate and targeting engineering of crossover vesicle-based gene delivery system

[Display omitted] •Exosome/biomimetic vesicles have crossover characteristic of bio-vesicles and liposomes.•Crossover vesicles can deliver gene with bio-distribution preference.•Liposome targeting modification can guide the engineering of crossover vesicles.•Source cell targeting modification can guide the engineering of crossover vesicles. Exosomes and biomimetic vesicles are widely used for gene delivery because of their excellent gene loading capacity and stability and their natural targeting delivery potential. These vesicles take advantages of both cell-based bioactive delivery system and synthetical lipid-derived nanovectors to form crossover characteristics. To further optimize the specific targeting properties of crossover vesicles, studies of their in vivo fate and various engineering approaches including nanobiotechnology are required. This review describes the preparation process of exosomes and biomimetic vesicles, and summarizes the mechanism of loading and delivery of nucleic acids or gene editing systems. We provide a comprehensive overview of the techniques employed for preparing the targeting crossover vesicles based on their cellular uptake and targeting mechanism. To delineate the future prospects of crossover vesicle gene delivery systems, various challenges and clinical applications of vesicles have also been discussed.