Influence of protein transduction domains on intracellular delivery of macromolecules.

Influence of protein transduction domains on intracellular delivery of macromolecules.
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DOI:
10.1517/17425247.3.6.739
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发表时间:
2006-11-01
影响因子:
6.6
通讯作者:
Dowdy, Steven F
Dowdy, Steven F
中科院分区:
医学2区
文献类型:
--
作者:
Murriel, Christopher L;Dowdy, Steven F

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由于质膜和血脑屏障选择性地将大多数化合物进入细胞的限制限制在 < 500 Da,因此直到最近,将大分子输送到细胞中还只是一个目标。然而,随着后基因组时代可用的治疗靶点的巨大努力,用于递送治疗性大分子的新方法正在迅速开发。小阳离子肽(称为肽/蛋白质转导结构域或细胞穿透肽)的发现,可以跨越生物膜,已成为一种古老的特洛伊木马,可将大的生物活性分子(例如肽、蛋白质和寡核苷酸)转运到体外哺乳动物细胞以及临床前模型和体内临床试验中。本综述讨论了肽/蛋白质转导域介导的大分子递送的影响及其作为重要的主要药物递送剂的可能用途。
As the plasma membrane and blood-brain barrier selectively restrict the entry of most compounds into cells to < 500 Da, delivering macromolecules into cells was, until recently, little more than a goal. However, with significant effort to capitalise on therapeutic targets available in the post-genomic era, novel approaches for delivering therapeutic macromolecules are being rapidly developed. The discovery of small cationic peptides, termed peptide/protein transduction domains or cell-penetrating peptides, which cross biological membranes, has emerged as a venerable Trojan horse to transport large, biologically active molecules, such as peptides, proteins and oligonucleotides, into mammalian cells in vitro, as well as in preclinical models and clinical trials in vivo. This review discusses the implications of peptide/protein transduction domain-mediated delivery of macromolecules and their possible uses as important primary drug delivery agents.