ANTISENSE AND KIDNEY

Antisense oligonucleotides are being used as gene-therapeutic agents. This short overview focuses on the in vivo kinetics and on potential i n vivo applications for research purposes as well as therapeutic appli cations. The most promising experimental results have been obtained wi th oligonucleotides targeted against genes involved in cell proliferat ion, such as c-myc, c-myb, Kras, and cdc-2. High parenteral doses of s uch oligonucleotides have limited growth of experimental tumors, and l ocal application of such oligonucleotides has limited neointimal proli feration in injured arteries. Therapeutic use of antisense in the kidn ey seems more distant. Because proximal tubule cells take up circulati ng oligonucleotides, transient suppression of proximal tubule message expression may be obtained following parenteral oligonucleotide admini stration. More sophisticated delivery systems, however, will be requir ed to achieve antisense efficacy over longer periods and in other comp artments of the kidney.