Cai Xiaojun, Dong Haiqing, Ma Junping, Zhu Haiyan, Wu Wei, Chu Meng, Li Yongyong, Shi Donglu
The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine, Shanghai 200092, P. R. China.
J Mater Chem B. 2013 Mar 28;1(12):1712-1721. doi: 10.1039/c3tb00425b. Epub 2013 Feb 8.
A spatial effect of targeted signal distribution is found in catiomer-gene polyplexes which strongly influences the gene transfection profiles. The nuclear localization sequence PKKKRKV (NLS) is chosen as the target ligand. For a given gene delivery system of constant composition, size, and charge, it is engineered such that the NLS is the only structural variable in polyplexes. This unique architecture of polyplexes relies on successive electrostatic interaction. The structural features of the PKKKRKV sequence in polyplexes are investigated by NMR. The gene transfection profiles of the polyplexes are found to be well correlated with the spatial distribution of the nuclear localization sequence. Upon modification of nuclear localization, the gene transfection efficiency is found to increase remarkably from 40% to 60%. The drastic improvement of gene transfection is explained by a NLS spatial distribution mechanism. High gene transfection based on spatial NLS distribution provides a new base for the design and development of non-viral gene delivery vectors.
在阳离子聚合物-基因复合物中发现了靶向信号分布的空间效应，这对基因转染情况有强烈影响。选择核定位序列PKKKRKV（NLS）作为靶向配体。对于给定的组成、大小和电荷恒定的基因递送系统，进行工程设计，使NLS成为复合物中唯一的结构变量。这种复合物的独特结构依赖于连续的静电相互作用。通过核磁共振研究复合物中PKKKRKV序列的结构特征。发现复合物的基因转染情况与核定位序列的空间分布密切相关。改变核定位后，基因转染效率从40%显著提高到60%。基因转染的显著改善由NLS空间分布机制解释。基于NLS空间分布的高基因转染为非病毒基因递送载体的设计和开发提供了新基础。
