Intracellular delivery of therapeutic proteins is highly challenging and in most cases requires chemical or genetic modifications. Herein, two complementary approaches for endocytosis‐independent delivery of proteins to live mammalian cells are reported. By using either a “glycan” tag naturally derived from glycosylated proteins or a “traceless” tag that could reversibly label native lysines on non‐glycosylated proteins, followed by bioorthogonal conjugation with cell‐penetrating poly(disulfide)s (CPDs), we achieved intracellular delivery of proteins (including antibodies and enzymes) which, upon spontaneous degradation of CPDs, led to successful release of their “native” functional forms with immediate bioavailability.

中文翻译：

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穿透细胞的聚二硫化物促进天然蛋白的细胞内递送

细胞内递送治疗性蛋白质极具挑战性，并且在大多数情况下需要化学或遗传修饰。本文报道了两种互补的方法，用于将蛋白不依赖内吞作用递送至活的哺乳动物细胞。通过使用天然衍生自糖基化蛋白的“聚糖”标签或可以可逆地标记非糖基化蛋白上的天然赖氨酸的“无痕”标签，然后与穿透细胞的聚二硫键（CPD）进行生物正交偶联，我们实现了蛋白质（包括抗体和酶）的细胞内传递，在CPD自发降解后，会导致其“天然”功能形式成功释放，并具有立即的生物利用度。