Phosphorothioate antisense oligonucleotides

Levin, A.A. 1999. A review of issues in the pharmacokinetics and toxicology of phosphorothioate antisense oligonucleotides. Biochim. Biophys. Acta 1489 69-84. 

Furhman, L., et al. 1995. Evaluation of several liposomal formulations and preparation techniques for the dermal delivery of phosphorothioate antisense oligonucleotides in hairless mouse skin in vitro. In AAPS Annual Meeting, Miami Beach, FL, USA. 

Deverre, J.R., Boutet, V., Boquet, D., Ezan, E., Grassi, J., and Grognet, J. M. (1997) A competitive enzyme hybridization assay for plasma determination of phosphodiester and phosphorothioate antisense oligonucleotides. Nucleic Acids Research, 25, 3584 3589. 

Clinical Trials with Other Phosphorothioate Antisense Oligonucleotides... 

Alahari, S.K. et al.. Inhibition of expression of the multidrug resistance-assodated P-glycoprotein of by phosphorothioate and 5 cholesterol-conjugated phosphorothioate antisense oligonucleotides. Mol Pharmacol, 50,808,1996. 

PO, PSs, PS, 20-mer antisense oligonucleotide complementary to the human c-myc mRNA with different intemucleotide linkages PO, phosphodiester PS3, three phosphorothioate linkages on both ends PS, phosphore thioate. RBC, red blood cells HSA, human serum albumin, a Yoshida el al., 1996 b Takakura et al., 1996 c Nishida et al., 1989. 

D.K. Monteith, and A.A. Levin. 1997. Antisense oligonucleotide inhibitors for the treatment of cancer 1. Pharmacokinetic properties of phosphorothioate oligodeoxynucleotides. Anti-Cancer Drug Design 12 383-393. 

J. Matson, H. Sasmor, L. Cummins, and A.A. Levin. 2003. Pharmacokinetics of a tumor necrosis factor-alpha phosphorothioate 2 -0-(2-methoxyethyl) modified antisense oligonucleotide comparison across species. Drug Metah. Dispos. 31 1419-1428. 

Yu, R.Z., J.Q. Su, J.S. Grundy, R.S. Geary, K.L. Sewell, A. Dorr, and A.A. Levin. 2003. Prediction of clinical responses in a simulated phase III trial of Crohn s patients administered the antisense phosphorothio-ate oligonucleotide ISIS 2302 comparison of proposed dosing regimens. Antisense Nucleic Acid Drug Dev. 13 57-66. 

Hoke GD, Draper K, Freier SM, et al. Effect of phosphorothioate capping on antisense oligonucleotide stability, hybridization and antiviral efficacy versus herpes simplex virus infection, Nucleic Acid Res 1991 20 5743-5748. 

Geary RS, Yu RZ, Siwkowski A. Pharmacokinetic/pharmacodynamic properties of phosphorothioate 2 -0-(2-methoxyethyl) modified antisense oligonucleotides in animals and man. In Crooke ST, ed. Antisense Drug Technology. New York Dekker, 2007. 

FIGURE 13 Small-scale separation of antisense oligonucleotides on Q modules. MA Q15 (Sarto-bind 15 cm2) flow rate 5 mL/min buffer A 20 m/Vt NaOH buffer B 20 mM NaOH plus 2.5 M NaCI sample 20 mer phosphorothioate crude, ISIS 2302 gradient 0- 100% B in 10 min. 

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