Antisense Oligonucleotides Strategy in the Treatment of Hypertension

Many kinds of drugs are used for the treatment of hypertension, but they are all short-acting (< or = 24 h) and patient compliance is poor. Gene therapy offers the advantage of producing long-term effects with high specificity, which should increase efficacy and reduce side effects. An antisense oligodeoxynucleotide (AS ODN) is a single-stranded oligonucleotide containing a gene-specific sequence of nucleotides, which is used to inhibit translation of mRNA. The application of AS ODNs for the treatment of hypertension began with targeting the renin-angiotensin system. Other genes, such as that coding for the beta1-adrenoceptor, have recently been targeted with AS ODNs in an attempt to reduce blood pressure. Strategies for the application of antisense technologies can be classified in two ways: the direct application of AS ODNs, and the production of AS by AS-cDNA inserted into viral vectors. Promising preclinical results from basic research have made feasible the possibility for antisense gene therapy of hypertension in the future.