Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 52, Issue 1, Pages 10-13Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm801294h
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The potency of second generation antisense oligonucleotides (ASOs) in anitnals was increased 3- to 5 -fold (ED(50) approximate to 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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