Genipin-Cross-Linked Thermophilic Histone-Polyethylenimine as a Hybrid Gene Carrier.
Genipin-Cross-Linked Thermophilic Histone-Polyethylenimine as a Hybrid Gene Carrier.
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DOI：
10.1021/acsmacrolett.5b00141
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发表时间：
2015-05
影响因子：
5.8
通讯作者：
Haobo Han;Hui Shi;Di Wu;Chunjie Li;Yan Zhang;Zhen Xing;W. Shi;Quanshun Li
中科院分区：
文献类型：
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作者：
Haobo Han;Hui Shi;Di Wu;Chunjie Li;Yan Zhang;Zhen Xing;W. Shi;Quanshun Li
通过京尼平介导的嗜热组蛋白与PEI 25 K的交联，成功构建了一种杂合基因载体HGP。从嗜热土芽孢杆菌HTA 426中克隆了嗜热组蛋白基因GK 2215，并在大肠杆菌BL 21中进行了高效表达。对嗜热组蛋白进行了系统的表征，然后用京尼平将其与PEI 25 K交联得到HGP。值得注意的是，由于这两种组分之间的协同作用，HGP表现出上级转染效率：PEI 25 K主要有助于pDNA的浓缩和转移，而嗜热组蛋白可以增强内体逃逸和进一步的核定位以实现高基因表达。同时，由于引入了无毒的嗜热组蛋白，HGP的细胞毒性和溶血活性比PEI 25 K低得多。此外，HGP还具有较强的内源性红色荧光。总之，蛋白质-聚合物混合载体可以潜在地用作治疗诊断递送系统，用于实现有效的基因治疗和体内成像。
A hybrid gene carrier, HGP, has been successfully constructed through the genipin-mediated cross-linking of thermophilic histone and PEI25K. The thermophilic histone gene GK2215 was cloned from Geobacillus kastophilus HTA426 and overexpressed in Escherichia coli BL21. The thermophilic histone was systematically characterized and then cross-linked with PEI25K by genipin to obtain HGP. Notably, HGP exhibited superior transfection efficiency due to the synergistic effects between these two components: PEI25K mainly contributed to the condensation and transfer of pDNA, while thermophilic histone could enhance the endosomal escape and further nuclear location to achieve high gene expression. Meanwhile, HGP showed much lower cytotoxicity and hemolytic activity than PEI25K due to the introduction of nontoxic thermophilic histone. In addition, a strong intrinsic red fluorescence could be obviously observed in HGP. In conclusion, the protein-polymer hybrid carrier could potentially be used as a theranostic delivery system for achieving both efficient gene therapy and in vivo imaging.