With the high efficacy of protein-based therapeutics and plenty of intracellular drug targets, cytosolic protein delivery in a cell-specific manner has attracted considerable attention in the field of precision medicine. Herein, we present an intracellular protein delivery system based on a target-specific repebody and the translocation domain of Pseudomonas aeruginosa exotoxin A. The delivery platform was constructed by genetically fusing an EGFR-specific repebody as a targeting moiety to the translocation domain, while a protein cargo was fused to the C-terminal end of the delivery platform. The delivery platform was revealed to efficiently translocate a protein cargo to the cytosol in a target-specific manner. We demonstrate the utility and potential of the delivery platform by showing a remarkable tumor regression with negligible toxicity in a xenograft mice model when gelonin was used as the cytotoxic protein cargo. The present platform can find wide applications to the cell-selective cytosolic delivery of diverse proteins in many areas.

中文翻译：

---

使用细菌外毒素的靶标特异性抗体和易位域的细胞内蛋白质递送系统

凭借基于蛋白质的疗法的高效功效和大量的细胞内药物靶标，以细胞特异性方式递送胞质蛋白已在精密医学领域引起了相当大的关注。在本文中，我们提出了一种基于靶标特异性复制体和铜绿假单胞菌易位域的细胞内蛋白质递送系统外毒素A.通过遗传融合EGFR特异性重链体作为易位域的靶向部分，构建转运平台，同时将蛋白货物融合到转运平台的C末端。揭示了该递送平台以靶标特异性方式有效地将蛋白质货物转运至胞质溶胶。我们通过显示显着的肿瘤消退，当将gelonin用作细胞毒性蛋白货物时，在异种移植小鼠模型中的毒性可忽略不计，证明了递送平台的实用性和潜力。本平台可在许多领域中广泛应用于多种蛋白质的细胞选择性细胞溶质递送。