Enhancement of the Inhibitory Activity of oatp Antisense Oligonucleotides by Incorporation of 2'-O,4'-C-Ethylene-Bridged Nucleic Acids (ENA) without a Loss of Subtype Selectivity

详细信息    查看全文

• 作者：Miho Takagi ; Koji Morita ; Daisuke Nakai ; Rie Nakagomi ; Taro Tokui ; and Makoto Koizumi
• 刊名：Biochemistry
• 出版年：2004
• 出版时间：April 20, 2004
• 年：2004
• 卷：43
• 期：15
• 页码：4501 - 4510
• 全文大小：208K
• 年卷期：v.43,no.15(April 20, 2004)
• ISSN：1520-4995

文摘

Antisense oligonucleotides (AONs) that specifically target the genes of rat organic aniontransporting polypeptide (oatp) subtypes were selected by using antisense in vitro selection (AIVS) anda conventional gene alignment program (GAP). When we incorporated several of our original 2'-O,4'-C-ethylene-bridged nucleic acid (ENA) residues into AONs, which were designed as gapmers containinga series of 2'-deoxynucleotides in the center, at both the 3' and 5' ends, the inhibitory activity of theseoatp AONs was enhanced and their inhibition was mediated by RNase H cleavage. Moreover, these ENAAONs did not lose their oatp selectivity. These strategies of using AIVS and GAP to select AONs followedby incorporation of ENA residues were effective for synthesizing oatp subtype-specific AONs.