利用TAT多肽增强腺病毒对细胞感染效率的研究

Improvement of Cellular Adenovirus Uptake with TAT Peptide is Cell-type Dependent

蛋白转导多肽本身或携带生物大分子能以一种不明机制的方式高效地穿过真核细胞质膜并且几乎没有组织选择性。这为生物药物研究、基因治疗等领域带来了新的希望。最近有研究表明:来源于HIV-1的TAT蛋白的蛋白转导结构域多肽可以显著地提高重组腺病毒感染细胞和实验动物的效率。在对。HeLa且和Vero-E62种具有不同病毒易感性的细胞进行重组腺病毒感染实验时发现TAT多肽可以明显地提高重组腺病毒对HeLa细胞的感染及在细胞中外源报道基因的表达,但是对Vero-E6细胞却没有效果,表明TAT多肽增强重组腺病毒的感染与靶细胞类型有关,而并不像转导现象那样没有组织差异。这为蛋白转导技术在病毒载体中的应用提供了参考,但其中涉及的蛋白转导的机制有待进一步实验研究。

In recent years, protein transduction technology has been regard as the most attractive development in macromolecular delivery. Through a currently unidentified mechanism, transduction peptide are capable of transducing biologically active cargo rapidly across plasma membrane into all tissues. The use of such peptide for drug and gene delivery is of great promise. Recent studies showed that a peptide, the protein transduction domain (PTD) from HIV-1 TAT protein, could improve cellular uptake and therapeutic gene delivery of recombinant adenovirus in cells and in vivo . This research was extended to HeLa and Vero-E6 cells, which have different susceptibility to virus infection. The TAT peptide significantly increased the adenovirus infection of HeLa cells but had no positive effect to Vero-E6 cells. It showed that the improvement of cellular adenovirus uptake with TAT peptide is cell-type dependent, which is different from the transduction of TAT-attached biologically active cargo. This phenomenon should be useful for various protocol of applying PTD to viral vector delivery, but more evidence is required to comprehend protein transduction.