Bremner K H, Seymour L W, Pouton C W
CRC Institute for Cancer Studies, University of Birmingham, Birmingham, B15 2TA, UK.
Curr Opin Mol Ther. 2001 Apr;3(2):170-7.
Inefficient transport of DNA from the cytoplasm into the nucleus remains a limiting step in the development of non-viral gene delivery systems. This is particularly acute in non-dividing cells, where entry to the nucleus is thought to occur only through the nuclear pore complex. Active import of physiological proteins is mediated by nuclear localization sequences (NLSs) within cargo proteins such as transcription factors. Here we review current knowledge of this import machinery and consider its exploitation by mammalian viruses. Significant research effort has been directed at incorporating NLSs into synthetic gene delivery systems to take advantage of this physiological pathway. Both non-covalent and covalent methods of conjugation are evaluated, with NLS linkage to both DNA and carrier, and compared with activities of simple cationic polymers. Finally, progress in the field of DNA sequence-specific nuclear import is examined and the current state of the technology assessed.
DNA从细胞质到细胞核的低效转运仍然是非病毒基因递送系统发展的一个限制步骤。这在非分裂细胞中尤为突出，在这类细胞中，进入细胞核被认为仅通过核孔复合体发生。生理蛋白的主动导入由诸如转录因子等货物蛋白内的核定位序列（NLS）介导。在此，我们综述了关于这种导入机制的现有知识，并探讨了哺乳动物病毒对其的利用情况。大量研究致力于将NLS整合到合成基因递送系统中，以利用这一生理途径。对非共价和共价偶联方法进行了评估，包括NLS与DNA和载体的连接，并与简单阳离子聚合物的活性进行了比较。最后，研究了DNA序列特异性核导入领域的进展，并评估了该技术的当前状态。
