Anti-sense oligonucleotides

M. Creek, and A.A. Levin. 1997. Pharmacokinetics and metabolism in mice of a phosphorothioate oligonucleotide anti-sense inhibitor of C-raf-1 kinase expression. Drug Metab. Dispos. 25 1272-1281. 

Mutation compensation Oligonucleotides Anti-sense SV40 TAGInhibition of dominant oncogenes Protocol pending... 

Boulm F., Freund F., Moreau S., Nielsen P.E., Gryaznov S., Toulme J.J., Litvak S. Modified (PNA, 2-O-methyl and phosphoramidate) anti-TAR anti-sense oligonucleotides as strong and specific inhibitors of in vitro HI.V.-l reverse transcription. Nucleic Acids Res. 1998 26 5492-5500. 

Anti-sense oligonucleotides Integrase inhibitors Rev inhibitors Tat antagonists... 

Dendrimers bearing certain fluorescent molecules attached on their periphery have been shown to be environmentally sensitive probes for the presence of certain metal ions or to changes in pH (Balzani et al., 2000 Paola et al., 2005). In addition, PAMAM dendrimers modified with the relatively hydrophobic dye Oregon Green 488 were shown to be a more effective transfection agent for anti-sense oligonucleotides than the dendrimer alone-plus the complex could be tracked within the cell due to the fluorescence of the dye (Yoo and Juliano, 2000). 

Often, it is desirable to block expression of particular genes that are activated by transcription factors. The anti-sense knockout experiments are directed toward this end and require the addition of an antisense oligonucleotide, which will anneal to the cis-acting regulatory element for a particular transcription factor in a specific gene. 

The uPA receptor also appears to play a role in cell locomotion and chemo-taxis, at least for human monocytes in vitro (G8). Using these cells, chemotaxis was inhibited by pretreatment with both anti-uPA receptor antibodies and anti-sense uPA receptor oligonucleotides. Expression of uPA catalytic activity was not required for chemotaxis with this cell type (G8). 

Fenske DB, Maurer N, Cullis PR. Encapsulation of weakly-basic drugs, anti-sense oligonucleotides and plasmid DNA within large unilamellar vesicles for drug delivery applications. In Torchilin VP, Weissig V, eds. Liposomes A Practical Approach. 2nd ed. Oxford Oxford University Press, 2002, Chapter 6. 

This review will not include immunological approaches to therapy, nor will it include any discussion of gene engineering, or the potential use of anti-sense oligonucleotides. 

PCR utilizes the enzymatic properties of a DNA polymerase to duplicate DNA through extension of a short, existing, double-stranded piece of DNA, usually 15-30 bp. This short, double-stranded DNA piece can be mimicked through addition of short oligonucleotides (primer) to each of the DNA strands, the sense (5 —3 ) and anti-sense (3 -5 ) primer. First, in the denaturing step, the DNA has to be... 

Voigt, M., et al. 2002. Down-regulation of NOSH gene expression by iontophoresis of anti-sense oligonucleotide in endotoxin-induced uveitis, Biochem Biophys Res Commun 295 336. 

Parenteral administration has been the preferred route because it allows complete systemic availability. Non-parenteral administration of antisense oligonucleotides is only made possible with the aid of novel formulations intended to overcome barriers to absorption (see Chapter 10). Similar to first-generation anti-sense oligonucleotides (ASOs), the pharmacokinetics of2 -MOE partially modified ASOs are characterized by ... 

S.T. Crooke. 1997. The influence of anti-sense oligonucleotide-induced RNA structure on E. coli RNase HI activity./. Biol. Chem. 272 18191-18199. 

P. Nicklin. 1996. Second-generation anti-sense oligonucleotides Structure-activity relationships and the design of improved signal transduction inhibitors. Biochem. Soc. Trans. 24 630-637. 

J. Matson, S. Murray, S. Booten, S. Bhanot, B. Monia, and R.S. Geary. 2003. effect of treatment regimen on sub-organ pharmacodynamics of a 2 -MOE modified anti-sense oligonucleotide, Isis 116847, targeting putative protein tyrosine phosphatase (PTEN) mRNA in rats. In AAPS Annual Meeting and Exposition. American Association of Pharmaceutical Scientists, Salt Lake City, UT. 

Bennett, C.F., M.-Y. Chiang, H. Chan, J.E.E. Shoemaker, and C.K. Mirabelli. 1992. Cationic lipids enhance cellular uptake and activity of phosphorothioate anti-sense oligonucleotides. Mol. Pharmacol. 41 1023-1033. 

C. York-Defalco, H. Sasmor, B. Conklin, and R.S. Geary. 2000. Absorption of anti-sense oligonucleotides in rat intestine effect of chemistry and length. Antisense Nucleic Acid Drug Dev. 10 35-44. 

Deverre JR, Boutet V, Boquet D, Ezan E, Grassi J, Grognet JM (1997) A competitive enzyme hybridization assay for plasma determination of phosphodiester and phosphorothioate anti-sense oligonucleotides. Nucleic Acids Res 25(18) 3584-3589... 

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