Antisense oligonucleotides phosphorothioate-based

Peng, B., Andrews, J., Nestorov, I., Brennan, B., Nicklin, P. and Rowland, M. (2001) Tissue distribution and physiologically based pharmacokinetics of antisense phosphorothioate oligonucleotide ISIS 1082 in rat. Antisense Nucleic Acid Drug Develop., 11, 15-27. 

The term (XG + Xc) is the sum of the mole fractions of guanine and cytidine in the antisense strand. The mole fraction of any nucleobase is equal to the number of nucleotides containing that base divided by the total number of nucleotides in the oligonucleotide strand. [M+] is the molar concentration of monovalent cations. In a typical mammalian cell, [K + ] is 140 mM, and [Na+ ] is 10 mM. L is the length of the duplex in base pairs. Based on Equation 6.2 and the assumption that phosphorothioate oligonucleotides behave as regular DNA, fomivirsen (6.17) would have a predicted Tm of 59 °C. Equation 6.1 predicts 64 °C. More complex forms of Equation 6.2 with increased accuracy appear regularly in the literature.8... 

Boado et al. [28] devised delivery systems based on conjugates of streptavidin and the 0X26 monoclonal antibody directed to the transferrin receptor as a carrier for the transport of ASO. These delivery systems were found to transport peptide nucleic acid antisense molecules, but not ASO, across the BBB. These authors attributed this difference to preferential binding of phosphorothioate oligonucleotide to plasma protein instead of the antibody complex, which reduced their transport. 

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... 

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