【文章名】Short Antisense Oligonucleotides with Novel 2'-4' Conformationaly Restricted Nucleoside Analogues Show Improved Potency without Increased Toxicity in Animals.
Short Antisense Oligonucleotides with Novel 2'-4' Conformationaly Restricted Nucleoside Analogues Show Improved Potency without Increased Toxicity in Animals.
作者
Seth, Punit P.;Siwkowski, Andrew;Allerson, Charles R.;Vasquez, Guillermo;Lee, Sam;Prakash, Thazha P.;Wancewicz, Edward V.;Witchell, Donna;Swayze, Eric E.;
[摘要]：The potency of second generation antisense oligonucleotides (ASOs) in animals was increased 3- to 5 -fold (ED50 u 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.
