RNASE H-MEDIATED INHIBITION OF TRANSLATION BY ANTISENSE OLIGODEOXYRIBO-NUCLEOTIDES - USE OF BACKBONE MODIFICATION TO IMPROVE SPECIFICITY

被引：57

作者：

LARROUY, B

BLONSKI, C

BOIZIAU, C

STUER, M

MOREAU, S

SHIRE, D

TOULME, JJ

机构：

[1] UNIV BORDEAUX 2,INSERM,CJF 90-13,BIOPHYS MOLEC LAB,BAT 3A,146 RUE LEO SAIGNAT,F-33076 BORDEAUX,FRANCE

[2] SANOFI ELF BIORECH,F-31676 LABEGE,FRANCE

来源：

GENE | 1992年 / 121卷 / 02期

关键词：

RABBIT GLOBIN MESSENGER RNA; METHYLPHOSPHONATE SANDWICH OLIGO; WHEAT GERM EXTRACT; PARTIAL COMPLEMENTARITY;

D O I：

10.1016/0378-1119(92)90121-5

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

A sequence of the rabbit alpha-globin mRNA is the primary target for ODN1, an unmodified 15-nucleotide (nt) antisense oligodeoxyribonucleotide (oligo). ODN1 prevented in vitro translation of both alpha- and beta-globin mRNAs in wheat germ extract. Nine secondary sites exhibiting more than 60% complementarity with ODN1 were present in the beta-globin message. The ODN1 inhibition of beta-globin synthesis was shown to be mediated by RNase H cleavage of the beta-globin mRNA at three partially complementary sites. Sandwich-type oligos consisting of a stretch of unmodified nt with a few methylphosphonate residues at both 5' and 3' ends were derived from ODN1. We have demonstrated that one such analogue (ODN2), with five phosphodiester linkages in the central region, exhibited improved specificity for alpha-globin mRNA compared with the unmodified parent 15-mer, due to a reduced ability of RNase H to cleave beta-mRNA/ODN2 mismatched duplexes.

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页码：189 / 194

页数：6

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