Definition for Antisense Technology
From Biology Forums Dictionary
Antisense refers to short DNA or RNA sequences, termed oligonucleotides, which are designed to be complementary to a specific gene sequence. The goal is to alter specific gene expression resulting from the binding of the antisense oligonucleotide to a unique gene sequence.
Antisense technology was first effectively used in plants to alter the levels of various degradative enzymes or plant pigments. The technology was rapidly applied to mammalian cells and in 1992 Science named antisense its runner-up in the molecule of the year award.
In principle, antisense technology is supposed to prevent protein production from a targeted gene. The exact mechanism by which this occurs remains uncertain. Proposed mechanisms include triplex formation, blocking RNA splicing, preventing transport of the mRNA antisense complex into the cytoplasm, increasing RNA degradation, or blocking the initiation of translation. Initially, cellular nucleases dramatically reduce the effectiveness of antisense oligonucleotides by rapidly degrading these molecules after administration. These obstacles can be overcome in applications utilizing synthetic oligonucleotides by altering the nature of the phosphodiester bond by replacing an oxygen with sulfur. Such modified oligonucleotides are termed phosphorothionates. Delivery of antisense oligonucleotides into target cells or the cell nucleus has been problematic. The variety of viral and non-viral delivery systems previously discussed are currently being explored to overcome this obstacle. Animals treated with antisense oligonucleotides have had significant side effects, some of which have been lethal. Currently, the most problematic aspect associated with antisense technology revolves around the specificity of their action. In some cases, non-specific antisense sequences, in other words, sequences which do not bind to the targeted gene or RNA, have prevented gene expression to the same degree as their sequence-specific antisense counterparts. This has led to considerable complication in data interpretation and requires detailed and careful data analysis before contemplation of clinical trials. Since antisense technology focuses on preventing gene expression, it has been most widely applied to cancer gene therapy.