Effect of Antisense Oligonucleotides Linked to Alkylating Agents on In Vitro Translation of Rabbit β-Globin andTypuaosomu bruceimRNAs

Abstract

Antisense oligonucleotides have been used to artificially regulate the expression of numerous genes, both in vitro and in vivo (I). Studies in cell-free extracts and in micro-injected frog oocytes have shown that oligomers complementary to the coding region cannot prevent polypeptide synthesis by the elongating ribosome, unless the RNA part of the oligonucleotide/RNA hybrid is degraded by RNase-H (2,3). Consequently, oligomers targeted downstream from the AUG initiation codon that do not elicit RNase-H activity do not inhibit protein synthesis. This was demonstrated to be the case for methylphosphonate and alpha derivatives, which are resistant to degradation by nucleases (4,5).