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Updated: Jun 27, 2026

Sequence-specific and Selective Recognition of Double-stranded RNAs over Single-stranded RNAs by Chemically Modified Peptide Nucleic Acids
Published on: September 21, 2017
Short antisense oligonucleotides with novel 2'-4' conformationaly restricted nucleoside analogues show improved
Punit P Seth1, Andrew Siwkowski, Charles R Allerson
1Isis Pharmaceuticals, 1891 Rutherford Road, Carlsbad, California 92008, USA. pseth@isisph.com
Abstract:
The potency of second generation antisense oligonucleotides (ASOs) in animals was increased 3- to 5 -fold (ED(50) approximately 2-5 mg/kg) without producing hepatotoxicity, by reducing ASO length (20-mer to 14-mer) and by employing novel nucleoside modifications that combine structural elements of 2'-O-methoxyethyl residues and locked nucleic acid. The ability to achieve this level of potency without any formulation agents is remarkable and likely to have a significant impact on the future design of ASOs as therapeutic agents.
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