Johnson Randolph M, Harrison Stephen D, Maclean Derek
KAI Pharmaceuticals, Inc, San Francisco, CA, 94080, USA.
Methods Mol Biol. 2011;683:535-51. doi: 10.1007/978-1-60761-919-2_38.
Since the discovery over 15 years ago of a protein transcription factor that possessed the ability to cross the plasma membrane, cell-penetrating peptides (CPPs) have been evaluated for the ability to transport diverse cargoes into cells, tissues, and organs. Certain CPPs have been used for the intracellular delivery of information-rich molecules to modulate protein-protein interactions and thereby inhibit key cellular mechanisms of disease. The ability to introduce drugs into cells allows the conventional biodistribution of drugs to be altered in order to favorably impact toxicity, patient compliance, and other treatment factors. In this monograph, we present the current status and future prospects for the application of CPPs to the development of human therapeutics. We discuss some of the advantages and disadvantages of using CPPs in the in vivo setting, and review the current status of a number of preclinical and human clinical studies of CPP-mediated delivery of therapeutics. These include CPP-conjugated moieties directed against a growing variety of targets and disease areas, including cancer, cardiology, pain, and stroke. Our discussion focuses on those therapeutics that have been tested in humans, including a CPP conjugate for the treatment of acute myocardial infarction. The promising results obtained in a number of these studies indicate that CPPs may have an important role in the development of novel therapeutics.
自15年前发现一种具有穿越质膜能力的蛋白质转录因子以来，人们一直在评估细胞穿透肽（CPPs）将各种物质运输到细胞、组织和器官中的能力。某些CPPs已被用于向细胞内递送富含信息的分子，以调节蛋白质-蛋白质相互作用，从而抑制疾病的关键细胞机制。将药物导入细胞的能力可改变药物的传统生物分布，从而对毒性、患者依从性和其他治疗因素产生有利影响。在本专著中，我们介绍了CPPs在人类治疗药物开发中的应用现状和未来前景。我们讨论了在体内使用CPPs的一些优缺点，并回顾了一些关于CPP介导的治疗药物递送的临床前和人体临床研究的现状。这些研究包括针对越来越多靶点和疾病领域（包括癌症、心脏病学、疼痛和中风）的CPP偶联部分。我们的讨论集中在那些已在人体中进行测试的治疗药物上，包括一种用于治疗急性心肌梗死的CPP偶联物。在许多这些研究中获得的有希望的结果表明，CPPs可能在新型治疗药物的开发中发挥重要作用。
