Short antisense oligonucleotides with novel 2′− 4′ conformationaly restricted nucleoside analogues show improved potency without increased toxicity in animals
PP Seth, A Siwkowski, CR Allerson… - Journal of medicinal …, 2009 - ACS Publications
PP Seth, A Siwkowski, CR Allerson, G Vasquez, S Lee, TP Prakash, EV Wancewicz…
Journal of medicinal chemistry, 2009•ACS PublicationsThe potency of second generation antisense oligonucleotides (ASOs) in animals was
increased 3-to 5-fold (ED50≈ 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.
increased 3-to 5-fold (ED50≈ 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.
The potency of second generation antisense oligonucleotides (ASOs) in animals was increased 3- to 5 -fold (ED50 ≈ 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.
ACS Publications