新型Bola两亲分子作为基因治疗药物输递载体的研究  

Research of a new bolaamphiphile as a gene therapy drug delivery vector

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作  者:孙丹丹[1,2] 刘洪梅[1,2] 李燕[1,2] 代凤英[1] 张欣[1] 

机构地区:[1]中国科学院过程工程研究所生化工程国家重点实验室,北京100190 [2]中国科学院研究生院,北京100049

出  处:《山东大学学报(理学版)》2012年第1期12-16,32,共6页Journal of Shandong University(Natural Science)

基  金:国家自然科学基金资助项目(51103159)

摘  要:为检测新型Bola两亲分子(Orn-C16-G)用作基因载体的性能,制备了Bola与siRNA的复合物(Bolaplexes),用原子力显微镜观察其在不同复合比下的形貌;并转染Hela细胞,用CCK-8检测Bolaplexes的细胞毒性,用荧光显微镜、流式细胞仪表征Bolaplexes的细胞内吞效果。实验结果显示,复合比1∶1条件下,Bola分子可以有效地压缩siRNA分子形成较小尺寸的复合物(100~200 nm)。Bolaplexes可高效地进入Hela细胞,并且毒性低于商售转染试剂,有较好的应用前景。本研究为下一步Bola两亲分子用于基因治疗的临床研究奠定了基础。To test the performance of new bolaamphiphile used as a gene carrier, compounds of the bola and siRNA-bo- laplexes were prepared. The morphology of bolaplexes at different weight ratios of bola and siRNA was observed with AFM ( Atomic force microscope). After Hela cells were transfected, the cytotoxicity of bolaplexes was detected with the CCK-8 kit, and the swallow effect was inspected with FM (fluorescence microscope) and FC (flow cyctometry). The result of AFM showed that at the condition of weight ratio of 1:1, the size of the bolaplexes was about 100 -200 nm, and they could access Hela cells through endocytosis with high efficiency. Toxic experimental results showed that the cytotoxicity of bolaplexes was inferior to that of the compounds of Lipofectamine2000TM and siRNA, so bolaplexes have a good prospect for applications. This study laid a foundation for the clinical study of bolaamphiphile used for gene therapy.

关 键 词:Bola两亲分子 基因治疗 非病毒载体 RNA干扰 

分 类 号:R945[医药卫生—微生物与生化药学]

 

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