Abstract

Antisense oligonucleotides are being used as gene-therapeutic agents. This short overview focuses on the in vivo kinetics and on potential in vivo applications for research purposes as well as therapeutic applications. The most promising experimental results have been obtained with oligonucleotides targeted against genes involved in cell proliferation, such as c-myc, c-myb, Kras, and cdc-2. High parenteral doses of such oligonucleotides have limited growth of experimental tumors, and local application of such oligonucleotides has limited neointimal proliferation in injured arteries. Therapeutic use of antisense in the kidney seems more distant. Because proximal tubule cells take up circulating oligonucleotides, transient suppression of proximal tubule message expression may be obtained following parenteral oligonucleotide administration. More sophisticated delivery systems, however, will be required to achieve antisense efficacy over longer periods and in other compartments of the kidney.