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  • Title: Not nonsense but antisense--applications of antisense oligonucleotides in different fields of medicine.
    Author: Oberbauer R.
    Journal: Wien Klin Wochenschr; 1997 Jan 31; 109(2):40-6. PubMed ID: 9123943.
    Abstract:
    This brief overview will give the reader an idea what antisense oligonucleotides are, how they act, what one can do with them, and what future perspectives might emerge. The idea behind this new therapeutic strategy is the selective blockage of a specific gene in vivo, which is responsible for a certain disease. Anti-sense oligonucleotides are short, traditionally 15 to 25 bases long, single stranded DNA fragments, which are targeted against a specific mRNA. This is the classical antisense mechanism. These DNA fragments can also be targeted against a specific genomic DNA sequence which is known as antigene therapy. The oligonucleotides have to be modified in order to increase their stability in vivo. Three mechanisms of action have been reported for the oligonucleotides: 1. Oligonucleotides are designed in a complementary (antisense) orientation to their target (sense) mRNA to which they hybridize in a strictly base pair specific manner (Watson-Crick base pairing) and thus block translation. 2. They can bind to the genomic DNA in the nucleus and thus block transcription (Hoogsten-type base triplets). A third, unspecific mechanism of action is the binding of the oligonucleotide to a target protein in what has been referred to as aptamer-binding. In addition, other nonspecific effects of cytokine and neutrophil activation were observed. The antisense strategy is a useful research tool for the identification of specific gene-protein functions. The first in vivo animal studies and clinical experiences have been carried out in the fields of cardiovascular medicine, oncology and virology yielding promising results. Currently, the first clinical trials using antisense oligonucleotides for the inhibition of gene expression are being performed; the results will be available in the next years.
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