ecules of antisense drug per cell exceeding the number of copies of RNA by several orders of magnitude. Thus, other factors must be rate limiting.

4.4 Activation of Double-Strand RNases

By the use of phosphorothioate oligonucleotides with 2'-modified wings and a ribonucle-otide center, we have shown that mammalian cells contain enzymes that can cleave double-stranded RNAs (157).This may be an important step forward because it adds to the repertoire of intracellular enzymes that may be used to cleave target RNAs, and because chimeric oligonucleotides 2'-modified wings and gaps have higher affinity for RNA targets than do chimeras with oli-godeoxynucleotide gaps.

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