ANTISENSE OLIGONUCLEOTIDES - GENE-REGULATION AND CHEMOTHERAPY OF AIDS

The use of antisense oligonucleotides in control of gene regulation and inhibition of virus replication is a unique approach designed to interfere with cell and virus replication, transcription and translation machinery at the molecular level. Extensive studies ave been carried out to regulate replication of human immunodeficiency virus by synthetic oligonucleotides and their several sugar phosphate backbone modified analogues. Thus far, studies have been carried out in tissue culture, and inhibition of HIV expression has been monitored by several parameters. Oligonucleotide phosphorothioates are effective in inhibiting HIV expression in tissue culture at a concentration of 1.10(-7) M, which translates into a dose of approximately 0.6 mg/kg bodyweight. A non-toxic dose of 100 mg/kg, in preliminary acute toxicity experiments, represents an exploitable therapeutic window for 'oligonucleotide therapy'.