申请人:National Institute of Advanced Industrial Science
and Technology
公开号:EP1731615A1
公开(公告)日:2006-12-13
It is intended to provide a modified DNA or RNA, the cytoplasmic localization of which has been established, and an siRNA, which is localized in the cytoplasm, shows a high activity and, therefore, is appropriately usable as a genetic drug, by using a means generally applicable to DNAs of various types regardless of original tissues. A cytoplasmic localization DNA or RNA modified with a peptide can be constructed by modifying a DNA fragment with an active hydrogen-containing group on a solid support, fusing a peptide having an active hydrogen-containing group therewith and then removing from the solid support. On the other hand, a cytoplasmic localization siRNA can be obtained by introducing chemical modification group(s) into the 5'-terminus of at least one of the sense chain and the antisense chain constituting the double-strand, or a dangling end of the antisense chain, or both of them.
本发明的目的是提供一种经修饰的 DNA 或 RNA(其细胞质定位已确定),以及一种 siRNA,这种 siRNA 定位于细胞质中,显示出很高的活性,因此可以适当地用作基因药物,其方法一般适用于各种类型的 DNA,与原始组织无关。用多肽修饰的细胞质定位 DNA 或 RNA 可以通过在固体支持物上修饰带有活性含氢基团的 DNA 片段,将带有活性含氢基团的多肽与之融合,然后从固体支持物上移除来构建。另一方面,将化学修饰基团引入构成双链的有义链和反义链中的至少一条链的 5'- 末端,或反义链的悬垂端,或它们两者的 5'- 末端,可以获得细胞质定位 siRNA。