Department of Chemistry , National University of Singapore , 117543 , Singapore.
NUS Graduate School for Integrative Sciences and Engineering , National University of Singapore , 117456 , Singapore.
J Am Chem Soc. 2018 Nov 28;140(47):15986-15996. doi: 10.1021/jacs.8b06584. Epub 2018 Nov 15.
Therapeutic proteins have increased dramatically in both number and frequency of use in recent years, primarily owing to advances in protein engineering. Protein therapy provides the advantages of high potency and specificity, as well as low oncogenic risks. To date, due to their inability to cross the plasma membrane into the intracellular space of mammalian cells, most therapeutic proteins can only target secreted modulators or extracellular receptors. The full potential of protein therapy is, however, being gradually realized by the development of various strategies capable of intracellular protein delivery. Notwithstanding, most of these strategies suffer from severe endosomal trapping, resulting in very low protein delivery efficiency. In this Perspective, we discuss various methods to directly transport proteins into the cell cytoplasm, thus bypassing the problems associated with endocytosis.
近年来，治疗性蛋白的数量和使用频率都显著增加，这主要归功于蛋白质工程的进步。蛋白质疗法具有高效力和特异性的优势，同时致癌风险较低。迄今为止，由于大多数治疗性蛋白无法穿过质膜进入哺乳动物细胞的细胞内空间，因此它们只能靶向分泌型调节剂或细胞外受体。然而，通过开发各种能够实现细胞内蛋白质递送的策略，蛋白质疗法的全部潜力正在逐渐实现。尽管如此，这些策略中的大多数都存在严重的内体捕获问题，导致蛋白质递送效率非常低。在本观点文章中，我们讨论了各种将蛋白质直接输送到细胞质中的方法，从而绕过与内吞作用相关的问题。
