Glycan arrays for analysis of influenza virus specificity

Approaches that improve upon the pharmacokinetic and pharmacodynamic properties of singlestrand antisense oligonucleotides are an active research topic. Antisense oligonucleotide phosphorothioates (ASOs) are highly protein bound. Therefore, it is likely that they traffic into and through cells via a protein to protein shuttling mechanism driven by binding affinity gradients.1 The ASO binding events are likely required for transport and uptake into cells, and it should be a saturable event. Nonlinear and saturable uptake has been reported in numerous in vivo pharmacokinetic studies in the literature.1 Additionally, it is clear from the literature reviewed that there are multiple ASO uptake mechanisms. It has been reported that co-administration of nonsense oligonucleotide improved potency of a 2'-O-(2-methoxyethyl) Gapmer ASO. 1 We investigated the effect of co-administration of nonsense oligonucleotide on the activity of cEt BNA ASO in mouse and rat. Co-administration of nonsense oligonucleotide significantly improved the potency of cEt BNA ASO in both mouse and rat. The tissue level of active drug was much lower while pharmacology was improved. This data suggests that a nonsense oligonucleotide can compete off the active ASO from the non-productive compartment and improve active ASO uptake into the productive compartment. Onset and duration of effect of active drug with and without nonsense oligonucleotide was similar. 1. Geary, R. S.; Wancewicz, E.; Matson, J.; Pearce, M.; Siwkowski, A.; Swayze, E.; Bennett, F. Biochemical Pharmacology 2009 , 78, 284-291. CARB 56 Structural characterization of unknown di-phosphorylated bovine submaxillary mucin O-