Intracellular Delivery of Native Proteins Facilitated by Cell-Penetrating Poly(disulfide)s
Intracellular Delivery of Native Proteins Facilitated by Cell-Penetrating Poly(disulfide)s
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DOI：
10.1002/anie.201711651
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发表时间：
2018-02-05
影响因子：
16.6
通讯作者：
Yao, Shao Q.
中科院分区：
文献类型：
--
作者：
Qian, Linghui;Fu, Jiaqi;Yao, Shao Q.
治疗性蛋白质的细胞内递送具有高度挑战性，并且在大多数情况下需要化学或遗传修饰。在此，两个互补的方法，用于不依赖内吞作用的蛋白质递送到活的哺乳动物细胞的报告。通过使用天然来源于糖基化蛋白质的“聚糖”标签或可以可逆地标记非糖基化蛋白质上的天然赖氨酸的无痕标签，随后与细胞穿透性聚赖氨酸进行生物正交缀合，利用二硫键（CPD），我们实现了蛋白质的细胞内递送（包括抗体和酶），在CPD自发降解后，导致其天然功能形式以立即生物利用度成功释放。
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.