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J Med Chem. 2009 Jan 8;52(1):10-3. doi: 10.1021/jm801294h.

Short antisense oligonucleotides with novel 2'-4' conformationaly restricted nucleoside analogues show improved potency without increased toxicity in animals.

Author information

1
Isis 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.

PMID:
19086780
DOI:
10.1021/jm801294h
[Indexed for MEDLINE]

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