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. 1995 Apr 11;23(7):1197–1203. doi: 10.1093/nar/23.7.1197

An assessment of the antisense properties of RNase H-competent and steric-blocking oligomers.

M A Bonham 1, S Brown 1, A L Boyd 1, P H Brown 1, D A Bruckenstein 1, J C Hanvey 1, S A Thomson 1, A Pipe 1, F Hassman 1, J E Bisi 1
PMCID: PMC306831  PMID: 7537874

Abstract

The antisense activity and gene specificity of two classes of oligonucleotides (ONs) were directly compared in a highly controlled assay. One class of ONs has been proposed to act by targeting the degradation of specific RNAs through an RNase H-mediated mechanism and consists of C-5 propynyl pyrimidine phosphorothioate ONs (propyne-S-ON). The second class of antisense agents has been proposed to function by sterically blocking target RNA formation, transport or translation and includes sugar modified (2'-O-allyl) ONs and peptide nucleic acids (PNAs). Using a CV-1 cell based microinjection assay, we targeted antisense agents representing both classes to various cloned sequences localized within the SV40 large T antigen RNA. We determined the propyne-S-ON was the most potent and gene-specific agent of the two classes which likely reflected its ability to allow RNase H cleavage of its target. The PNA oligomer inhibited T Ag expression via an antisense mechanism, but was less effective than the propyne-S-ON; the lack of potency may have been due in part to the PNAs slow kinetics of RNA association. Interestingly, unlike the 2'-O-allyl ON, the antisense activity of the PNA was not restricted to the 5' untranslated region of the T Ag RNA. Based on these findings we conclude that PNAs could be effective antisense agents with additional chemical modification that will lead to more rapid association with their RNA target.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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