R3V6 Amphiphilic Peptide with High Mobility Group Box 1A Domain as an Efficient Carrier for Gene Delivery
R3V6 Amphiphilic Peptide with High Mobility Group Box 1A Domain as an Efficient Carrier for Gene Delivery
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具有高迁移率 Group Box 1A 结构域的 R3V6 两亲性肽作为基因传递的有效载体
DOI：
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发表时间：
2013
期刊：
影响因子：
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通讯作者：
Minhyung Lee
中科院分区：
文献类型：
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作者：
J. Ryu;Pureum Jeon;Minhyung Lee
R3 V6肽包括亲水性精氨酸段和疏水性缬氨酸段。在先前的研究中，R3 V6肽被评估为基因载体，并被发现具有低细胞毒性。然而，在N2 A神经母细胞瘤细胞中，R3 V6的转染效率低于多聚-L-赖氨酸（PLL）。在本研究中，R3 V6与高迁移率族蛋白1A结构域（HMGA）的组合提高了转染效率。HMGA来源于核蛋白，具有许多带正电荷的氨基酸。因此，HMGA通过电荷相互作用与DNA结合。此外，HMGA具有核定位信号肽，并且可以增加DNA进入细胞核的递送效率。制备具有HMGA、R3 V6和DNA的三元复合物，并作为基因载体进行评价。首先，制备具有负表面电荷的HMGA/DNA复合物。然后，将R3 V6加入到复合物中以包覆HMGA/DNA复合物的负电荷，形成HMGA、R3 V6和DNA的三元复合物。物理表征研究表明，三元复合物比PLL/DNA复合物更稳定。在N2 A细胞中，HMGA/R3 V6/DNA复合物具有比PLL/DNA、HMGA/DNA或R3 V6/DNA复合物更高的转染效率。此外，HMGA/R3 V6/DNA复合物对细胞没有毒性。因此，HMGA/R3 V6/DNA复合物可能是一种有用的基因传递载体。
The R3V6 peptide includes a hydrophilic arginine stretch and a hydrophobic valine stretch. In previous studies, the R3V6 peptide was evaluated as a gene carrier and was found to have low cytotoxicity. However, the transfection efficiency of R3V6 was lower than that of poly-L-lysine (PLL) in N2A neuroblastoma cells. In this study, the transfection efficiency of R3V6 was improved in combination with high mobility group box 1A domain (HMGA). HMGA is originated from the nuclear protein and has many positively-charged amino acids. Therefore, HMGA binds to DNA via charge interaction. In addition, HMGA has a nuclear localization signal peptide and may increase the delivery efficiency of DNA into the nucleus. The ternary complex with HMGA, R3V6, and DNA was prepared and evaluated as a gene carrier. First, the HMGA/DNA complex was prepared with a negative surface charge. Then, R3V6 was added to the complex to coat the negative charges of the HMGA/DNA complex, forming the ternary complex of HMGA, R3V6, and DNA. A physical characterization study showed that the ternary complex was more stable than the PLL/DNA complex. The HMGA/R3V6/DNA complex had a higher transfection efficiency than the PLL/DNA, HMGA/DNA, or R3V6/DNA complexes in N2A cells. Furthermore, the HMGA/R3V6/DNA complex was not toxic to cells. Therefore, the HMGA/R3V6/DNA complex may be a useful gene delivery carrier.