Effect of monomer sequence of poly(histidine/lysine) catiomers on gene packing capacity and delivery efficiency
Effect of monomer sequence of poly(histidine/lysine) catiomers on gene packing capacity and delivery efficiency
复制标题
聚组氨酸/赖氨酸阳离子异构体单体序列对基因包装能力和递送效率的影响
DOI：
10.1039/c4ra13785j
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发表时间：
2015-01
期刊：
影响因子：
3.9
通讯作者：
Li Yongyong
中科院分区：
文献类型：
--
作者：
Zhou Jiashan;Li Yan;Dong Haiqing;Yuan Hua;Ren Tianbin;Li Yongyong
高分子化合物作为一种能够模拟病毒进行基因包装和传递的非病毒载体，在基因治疗中受到了广泛的关注。受结构单元序列在各种生物分子（包括DNA和蛋白质）中至关重要的作用的启发，在本研究中，我们打算研究聚合物阳离子聚合物的单体序列如何影响其基因包装能力和递送效率。选择文献报道较多的组氨酸-赖氨酸共聚物作为基因载体的支架材料。合成了四种基于序列调控肽单体的可还原聚阳离子（RPC）。除单体序列外，四种RPC的化学参数（即组成和分子量）均控制在可比水平。所有的RPC都表现出较低的细胞毒性和有效的DNA结合能力。然而，这些RPC显示出明显的差异，特别是在它们的DNA结合能力，缓冲能力和转染效率。以293 T细胞为模型，我们发现聚阳离子单体序列的调控可以显著影响其基因传递性能，差异达100倍。这种序列效应可能与RPC/pDNA复合物的不同链折叠方式及理化性质有关，为设计具有良好基因治疗前景的基因载体提供了新的思路。
Polymeric catiomers, which can mimic viruses for gene packing and delivery, have received considerable attention as nonviral vectors for gene therapy. Inspired by the critically important role of the sequence of structural units in various biomolecules, including DNA and protein, in this study, we intend to investigate how the monomer sequence of a polymeric catiomer affects its gene packing capacity and delivery efficiency. The well-documented poly(histidine-co-lysine) was chosen as the scaffold for gene carrier. Four reducible polycations (RPCs) based on sequence-regulated peptides monomers were synthesized. Chemical parameters (namely, composition and molecular weight) of four RPCs were controlled at comparable level except for the monomer sequence. All of the RPCs exhibited low cytotoxicity and effective DNA binding ability. However, these RPCs displayed distinct diversity from each other, especially in their ability of binding to DNA, buffering capacity and transfection efficiency. Using 293T cell as the mode, we found that the regulation of the monomer sequence of polycations could significantly affect their properties for gene delivery, with differences of 100 fold. The sequence effect might be correlated with different chain folding as well as physiochemical properties of RPCs/pDNA complexes, providing new insight for designing gene vector with promising prospects in gene therapy.
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影响因子：
6.2
作者：
Zhou, Huofei;Yu, Weiting;Ma, Xiaojun
通讯作者：
Ma, Xiaojun
影响因子：
3.7
作者：
Moyer CL;Nemerow GR
通讯作者：
Nemerow GR
影响因子：
15
作者：
Liu, YM;Reineke, TM
通讯作者：
Reineke, TM
影响因子：
14.9
作者：
Read ML;Singh S;Ahmed Z;Stevenson M;Briggs SS;Oupicky D;Barrett LB;Spice R;Kendall M;Berry M;Preece JA;Logan A;Seymour LW
通讯作者：
Seymour LW
影响因子：
10.8
作者：
Godbey, WT;Mikos, AG
通讯作者：
Mikos, AG