Membrane-Fusogenic Nanoparticles for Gene and Cell Therapy.

Abstract

Inspired by natural membrane-fusion processes, membrane-fusogenic nanoparticles have emerged as a versatile platform for precise and efficient therapeutic delivery. By fusing directly with target cells, these systems efficiently transfer encapsulated bioactive cargo into the cytoplasm while bypassing endosomal entrapment. Simultaneously, the fusion process enables direct membrane engineering by integrating functional agents into the cell surface through lipid mixing. Leveraging this dual capability, membrane-fusogenic nanoparticles are evolving from simple gene delivery vehicles to versatile tools for cell engineering. In this Mini-Review, we highlight recent advances that position these nanoparticles as a unified platform bridging gene therapy and cell therapy. We outline the design principles and fusion-inducing mechanisms of current membrane-fusogenic nanoparticles and then discuss recent developments in programmable functionalization for gene and cell therapies. Finally, we address current challenges and future perspectives, offering insights into guiding the further optimization and clinical translation of these systems.