Abstract

A critical problem in assessing the physiological role of the sodium–calcium exchanger (NCX) in arterial and cardiac myocytes (and other types of cells) has been the absence of a selective and specific blocker. Antisense oligodeoxynucleotides (AS-ODNs) have great potential for the inhibition of specific gene expression in cells. In theory, AS-ODNs inhibit gene expression by Watson–Crick base pair binding to the complementary ribonucleic acid (RNA) sequences, thereby preventing translation of the messenger RNA (mRNA). Inhibition of gene expression, which results from hydrogen bonding between nucleic acid bases from the sense (mRNA) and antisense (AS-ODN) sequence, should be highly specific, given a long enough AS-ODN. The haploid human genome contains about 3 × 10 9 bases. A random sequence of 17 nucleotides long or longer would have a low probability of occurring more than once and therefore a high probability of being unique. Thus, antisense strategies have the potential for sensitive and selective inhibition of the NCX expression.

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