INHIBITION OF VIRAL GENE-EXPRESSION BY HUMAN RIBONUCLEASE-P

External guide sequences (EGSs) are small RNA molecules which consist of a sequence complementary to a target mRNA and render the target RNA susceptible to degradation by ribonuclease P (RNase P). EGSs were des igned to target the mRNA encoding thymidine kinase (TK) of herpes simp lex virus 1 for degradation. These EGSs were shown to be able to direc t human RNase P to cleave the TK mRNA sequence efficiently in vitro. A reduction of about 80% in the expression level of both TK mRNA and pr otein was observed in human cells that steadily expressed an EGS, but not in cells that either did not express the EGS or produced a ''disab led'' EGS which carried a single nucleotide mutation that precluded RN ase P recognition. Thus, EGSs may represent novel gene-targeting agent s for inhibition of gene expression and antiviral activity.