Additive antisense effects of different PNAs on the in vitro translation of the PML/RARα gene

Abstract

The potential use of peptide nucleic acid (PNA) as a sequence-specific inhibitor of RNA translation is investigated in this report. Three different regions of the PML/RARα oncogene, including two AUG potential start codons, were studied as targets of translation inhibition by antisense PNA in a cell-free system. A PNA targeted to the second AUG start codon, which was shown previously to be able to suppress in vitro translation from that site completely, was used alone or in combination with another PNA directed to the first AUG, and a third RNA within the 5'-untranslated region (5'-UTR) of mRNA. When used alone, no PNA was able to completely block the synthesis of the PML/RARα protein. The 5'-UTR RNA was the most potent translation inhibitor when used as single agent. However, a near complete (≤ 90%) specific inhibition of the PML/RARα gene was obtained when the three PNAs were used in combination, thus obtaining an additive antisense effect.