Phosphorothioate antisense therapies

Among DNA-based drugs, only antisense DNA is currently analyzed by capillary electrophoresis. Antisense DNA therapy requires reliable and convenient methods for sequencing short single-stranded oligonucleotides. A method for phosphorothioate antisense DNA sequencing by capillary electrophoresis coupled to UV detection has been developed based on a modified chain-termination sequencing method.Capillary gel electrophoresis alone or in combination with HPLC is also used for pharmacokinetics study of antisense... 

Oligonucleotides are only very poorly taken up into cells, and a variety of conjugates have been studied with the aim of improving cellular uptake. The cellular uptake of the ISIS ICAM-1-specific phosphorothioate ODN conjugated to cholesterol (ISIS-9388) has been studied in vivo for uptake into liver cells in rats." The presence of the 3 -cholesterol on the ODN resulted in a two-fold increase in accumulation of the ODN in various liver cell types, and the authors conclude that conjugation of ODNs with cholesterol is likely to be beneficial for antisense therapy of liver-associated diseases. ODNs which have 3 -linked cholesterol have been shown to interact with cell membranes in macrophages, and... 

Deoxyribonucleotides, deoxyribonucleotide phosphorothioates, modified DNA, and analogs have wide applications in molecular biology, antisense applications, antigene therapy, etc. Three methods are available for the synthesis of oligonucleoside phosphorothioates phosphoramidite, H-phosphonate, and phospho-... 

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