Oligonucleotides design

Oblimersen sodium is a DNA antisense oligonucleotide designed to specifically bind to human bcl-2 mRNA, resulting in catalytic degradation of bcl-2. This results in decreased translation of the protein Bcl-2, which is a cellular antiapoptotic protein. Thus, oblimersen enhances sensitivity to chemotherapy by shifting the intracellular balance to a state in which the cells are more likely to be killed by apoptosis. Currently, it is used in combination chemotherapy for treating advanced melanoma. 

Mishra, R.K., Le Tinevez, R. and Toulme, J.J. (1996) Targeting nucleic acid secondary structures by antisense oligonucleotides designed through in vitro selection. Proc. Natl. Acad. Sci. USA, 93, 10679-10684. 

Sequence comparison with those reported in the protein bank comparison of experimentally determined and predicted MW and pi amino acid sequence to determine function oligonucleotides design for gene search. 

Table 1 Oligonucleotides designed for evaluating the effects of mismatches on ligation...

Table 3 Oligonucleotides designed in the detection of mutations by SOLAC ...

Background Basic Properties of LNA Biophysical Properties of LNA LNA Oligonucleotide Designs Biochemical Properties of LNA LNA Applied in Vitro Pharmacology Inhibition of MicroRNA... 

Primer— A short oligonucleotide designed to anneal to single-stranded DNA and from which DNA polymerase can add deoxynucleotide triphosphate (dNTPs) in a complementary fashion to the template DNA. A primer pair flanks the target DNA to be amplified in PCR and creates the specificity of the reaction. 

Antisense oligonucleotides administered intraventricularly have been reported to induce a variety of effects in the CNS. Intraventricular injection of antisense oligonucleotides to neuropeptide-y-yl receptors reduced the density of the receptors and resulted in behavioral signs of anxiety (226). Similarly, an anti-sense oligonucleotide designed to bind to NMDA-Rl receptor channel RNA inhibited the synthesis of these channels and reduced the volume of focal ischemia produced by occlusion of the middle cerebral artery in rats (226). 

A phosphorothioate oligonucleotide designed to inhibit human PKC-a expression selectively inhibited expression of PKC-a RNA and PKC-a protein in human tumor cell lines implanted subcutaneously in nude mice after intravenous administration (236). In these studies, effects on RNA and protein levels were highly specific and observed at doses lower than 6 mg/kg. A large number of control oligonucleotides failed to show activity. 

Finally, a single injection of a phosphorothioate oligonucleotide designed to inhibit c-AMP-dependent protein kinase type 1 was reported to selectively reduce RNA and protein levels in human tumor xenografts and to reduce tumor growth (239). 

V itravene, a phosphorothioate oligonucleotide designed to inhibit cytomegalovirus-induced retinitis, has been shown to be safe and effective in the treatment of this disease after in-travitreal injection and has been approved for sale by regulatory agencies in the United States, Europe, and South America (for review, see Ref 240). 

Purely molecular biological approaches have also yielded some success in identifying putative G-protein subunits. Ma et al. [89] utilised oligonucleotides designed with reference to conserved regions of G subunits and via PCR amplification, generated a... 

Henry SP, Templin MV, Gillett N, et al. Correlation of toxicity and pharmacokinetic properties of a phosphorothioate oligonucleotide designed to inhibit ICAM-1. Toxicol Pathol 1999 27 95-100. 

The structure of an oligonucleotide designed to assemble a 4-way junction has been investigated by Preliminary results in the structure determination of nucleic acid analogues containing... 

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