一种源自细菌注射系统的可重编程的蛋白质递送工具

A programmable protein delivery tool derived from bacterial syringe

Methods of manipulating protein in cells are of great value in research and clinical therapies.Indirect methods,such as plasmid and mRNA transfection,and virus-based delivery,have been important skills of life science and medical researchers.Although extensively applied,these nucleic-acids-based approaches are limited by many shortcomings[1].It is very difficult to precisely manipulate the expression level and timeframe of the objective protein in host cells in these methods.The intracellular stabilities of the plasmids or mRNAs that encode the objective genes are affected by several factors,including gene sequence,three-dimensional structure,host nucleases and their delivery processes.These indirect methods require the host transcriptional and translational systems for protein synthesis.However,the transcription and translation machines are tightly regulated by host signaling.In addition,the immunogenicity of DNAs and viral vectors,and the safety of the lipid nanoparticles for mRNA transfection are obstacles of these indirect methods in many clinical applications[2].In contrast,direct protein delivery with target-cell specificity is more efficient in controlling the quantity and function of the protein of interest.However,due to the hydrophobicity of plasma membrane and high molecular weights of proteins,it remains a great challenge to direct deliver protein into target cells across the intact plasma membrane.