antisense

antisense DNA or RNA manipulated in a laboratory so that its components (nucleotides) form a complementary copy of normal, or "sense," messenger RNA (mRNA; see nucleic acid ). Antisense techniques are used to deactivate disease-causing or undesirable genes so that they cannot produce harmful or unwanted proteins. (Conventional drugs bind directly with disease-causing protein molecules, but their imperfect specificity may lead them to bind with other protein molecules, resulting in unwanted side effects. Antisense molecules are extremely specific.) In some applications of this technique, the antisense nucleic acid segment is inserted into an inactivated or nonvirulent virus, then introduced into the cell. The antisense segment pairs with the mRNA, preventing the synthesis of protein by the mRNA. Antisense has applications in agricultural biotechnology, where it has been used to deactivate the gene that causes softening in tomatoes, and in medicine, especially in cancer and antiviral therapy. See also gene therapy .

antisense RNA An RNA molecule whose base sequence is complementary to that of the RNA transcript of a gene, i.e. the ‘sense’ RNA, such as a messenger RNA (mRNA). Hence, an antisense RNA can undergo base pairing with its complementary mRNA sequence. This blocks gene expression, either by preventing access for ribosomes to translate the mRNA or by triggering degradation of the double-stranded RNA by ribonuclease enzymes. Like antisense DNA, antisense RNA has therapeutic potential for modifying the activity of disease-causing genes. Also, genes encoding antisense RNAs can be used in genetic engineering to alter the makeup of organisms. For example, the FlavrSavr tomato was engineered with an artificial gene for antisense RNA that prevented expression of a gene for an enzyme involved in ripening, in order to retard spoilage. In the 1980s it was discovered that double-stranded RNA molecules have a much greater ability to suppress their corresponding genes than single-stranded RNAs, due to a phenomenon called RNA interference. This is now the focus of much research.

antisense DNA A single-stranded DNA molecule that can bind to a complementary base sequence in a particular messenger RNA (mRNA) molecule and so prevent synthesis of the protein encoded by the mRNA. Antisense DNA thus has the potential to block the expression of a particular gene, hence its potential as a therapeutic weapon to combat certain diseases. A short DNA strand, called an antisense oligodeoxynucleotide (ODN), is constructed consisting of 15–20 deoxynucleotides complementary to a segment of the target mRNA. By binding to the mRNA, the ODN may either prevent translation of the mRNA by ribosomes or trigger degradation of the mRNA by cellular enzymes. To be effective drugs, ODNs have to be chemically modified to resist degradation by DNase enzymes and must be attached to some kind of vector that will deliver them to the target cells. An antisense ODN product has already been approved in the USA for the treatment of cytomegalovirus infections of the eye. See also antisense RNA.