Antisense inhibition of the Renin-Angiotensin system

Antisense inhibition has been developed, particularly in cell-culture applications, to the point where it is being tested in clinical trials for HIV and cancer (1,2). The pros and cons of its use have been reviewed elsewhere (3). Before 1992, however, antisense (AS) had not been applied in vivo with any success. There was much concern about the efficiency of cellular uptake of oliogodeoxynucleotides (ODNs). During 1992-1993, a few laboratories simultaneously and independently designed AS-ODNs and tested them in the brain (4-8). Cellular uptake was not a limiting factor in the central nervous system.