Repurposing bacterial toxins for intracellular delivery of therapeutic proteins
Repurposing bacterial toxins for intracellular delivery of therapeutic proteins
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DOI：
10.1016/j.bcp.2017.04.009
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发表时间：
2017-10-15
影响因子：
5.8
通讯作者：
Melnyk, Roman A.
中科院分区：
文献类型：
--
作者：
Beilhartz, Greg L.;Sugiman-Marangos, Seiji N.;Melnyk, Roman A.
尽管付出了巨大的努力，在哺乳动物细胞内实现有效的蛋白质水平仍然是基于生物制剂的药物发现和开发的最大挑战之一。蛋白质无法轻易穿过生物膜，从而阻碍了哺乳动物细胞内丰富的细胞内靶标和应用。现有的递送方法通常存在无法靶向特定细胞和组织、内体逃逸差以及体内功效有限的问题。本评论的目的是强调某些类别的细菌毒素的潜力，这些毒素在以高亲和力结合宿主细胞表面受体后，自然地将大蛋白质递送到靶细胞的胞质室中，作为强大的蛋白质递送平台。我们回顾了近年来在展示这些系统在提供各种蛋白质货物方面的效用方面所取得的进展，特别关注三个不同的基于毒素的平台。我们认为，随着蛋白质去免疫策略的最新进展，细菌毒素有望将生物制剂引入细胞的内部密室，并用新一代疗法治疗大量迄今为止无法治疗的疾病。 (C) 2017 Elsevier Inc. 保留所有权利。
Despite enormous efforts, achieving efficacious levels of proteins inside mammalian cells remains one of the greatest challenges in biologics-based drug discovery and development. The inability of proteins to readily cross biological membranes precludes access to the wealth of intracellular targets and applications that lie within mammalian cells. Existing methods of delivery commonly suffer from an inability to target specific cells and tissues, poor endosomal escape, and limited in vivo efficacy. The aim of the present commentary is to highlight the potential of certain classes of bacterial toxins, which naturally deliver a large protein into the cytosolic compartment of target cells after binding a host cell-surface receptor with high affinity, as robust protein delivery platforms. We review the progress made in recent years toward demonstrating the utility of these systems at delivering a wide variety of protein cargo, with special attention paid to three distinct toxin-based platforms. We contend that with recent advances in protein deimmunization strategies, bacterial toxins are poised to introduce biologics into the inner sanctum of cells and treat a wealth of heretofore untreatable diseases with a new generation of therapeutics. (C) 2017 Elsevier Inc. All rights reserved.