Ribozyme cleavage of 5 alpha -reductase mRNA

摘要

The steroid enzyme 5 alpha -reductase is responsible for the conversion of testosterone to the more-potent androgen dihydrotestosterone (DHT). The catalytic cleavage of nucleic acid encoding 5 alpha -reductase by a ribozyme which selectively recognizes such nucleic acid reduces the level of expression of 5 alpha -reductase by mammalian cells including human cells treated with such ribozyme. The reduction of nucleic acid (e.g. mRNA) levels leads to a corresponding reduction of enzyme levels and dihydrotestosterone levels in surrounding tissues, thus providing a therapeutic effect. The transformation of 5 alpha -reductase producing cells with an expression vector containing a structural gene for a ribozyme is shown to decrease 5 alpha -reductase expression. Pharmaceutical compositions and methods useful for topically administering effective amounts of such a ribozyme to hair follicle cells also are exemplified.