Antisense Oligonucleotides for in Vivo Studies of Angiotensin Receptors
Synthetic antisense (AS) oligodeoxynucleotides inhibit genetic expression by sequence-specific hybridization to mRNA that renders the mRNA inactive for translation. We have been using AS oligos to lower blood pressure by inhibiting angiotensin receptors and angiotensinogen in freely moving, whole animals. This recent application of antisense technology to in vivo studies, opens a new way of approaching physiological problems with the precision of molecular biology. The possibility of blocking specific gene expression by AS inhibition without multiple, non-specific side effects has potential for therapeutic uses in many diseases. Antisense inhibition is an extremely attractive pharmacological and investigative approach since it offers base-to-base specificity to the target protein and versatility appropriate to the complexity of the genetic code. However, there are a number of issues to be considered before using antisense in any experimental or clinical setting. These include (1) selection of target sequence, (2) the mechanism of cellular uptake, (3) stability of antisense oligos in cells and body fluids, (4) possible intracellular sites of action and (5) effectiveness, in terms of specificity, and duration of action.
KeywordsCellular Uptake Antisense Oligonucleotide Receptor mRNA Antisense Inhibition Anti Sense Oligonucleotide
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