Use of ribozymes for functionating genes

Double stranded DNAs, expression vectors and methods for their use are provided in which the intracellular expression of the double stranded DNAs is used to alter the phenotype of a target cell so that the function of a target nucleic acid that includes a nucleotide sequence encoding a motif of interest can be determined using a combinatorial ribozyme library. The members of the library are catalytic RNAs that disrupt the expression of the transcription product of the target nucleic acid. Disruption of transcription product expression results in an altered cell phenotype which is used to determine the function of the target nucleic acid. The specific phenotype or response may be associated with normal cellular processes, or it may contribute to the generation of pathogenesis involved in disease development. The compositions find use in high-throughput screens to assign gene functions. When associated with a pathogenic phenotype, these genes or their gene products can constitute therapeutic targets for treatment of diseases. The complete sequence of the gene containing the target nucleic acid need not to be known for the method to be used successfully.