TAT蛋白转导域：蛋白质治疗的新曙光

TAT蛋白转导域是源自人类免疫缺陷病毒Tat蛋白的一段碱性氨基酸多肽，能够将与之共价连接的多肽、蛋白、核酸等生物大分子快速而高效地转导入细胞内部，在药物转运和疾病治疗等领域有着巨大的应用潜力.TAT蛋白转导域首先通过电荷相互作用吸附于细胞膜，然后通过脂筏介导的巨胞饮作用进入细胞.随着体外研究的不断成熟，应用TAT蛋白转导域治疗人类肿瘤、卒中、炎症等疾病的动物模型也获得了成功，TAT蛋白转导域进入临床指日可待.

TAT Protein Transduction Domains:New Promise for Protein Therapy

Intracellular delivery of biologically active macromolecules remains problematic because of the bioavailability restriction imposed by the cell membrane. The cationic 11-amino acid fragment derived from human immunodeficiency type 1 (HIV-1) tat protein, termed TAT protein transduction domain, has proven to be an invaluable tool to deliver a wide variety of macromolecules across the plasma membrane and into intact tissues. TAT-fusion proteins are rapidly internalized by lipid-raft-mediated macropinocytosis after an initial ionic interaction, enabling previously unavailable large molecules to modulate in vivo biology and alleviate disease. Recent applications of TAT protein transduction to treat multiple preclinical models of human diseases offer an exciting opportunity for the development of protein therapies. Time is drawing near for the design of clinical trials using TAT fusion proteins.