Method of isolating ribozyme targets

A method for in vivo selection of a ribozyme active on a defined RNA target, comprising the steps of:

• introducing a first population of ribozymes, in which each said ribozyme has a different substrate binding arm, into a second population of cultured cells, wherein said ribozymes are formed from a third population of fragmented target DNA molecules encoding said RNA target into each of which an enzymatic portion of a ribozyme is inserted;
• providing said RNA target to said second population of cultured cells, and
• identifying those cells which contain a ribozyme active at the RNA target;
• wherein said third population is formed by fragmenting target DNA encoding said defined RNA target with DNAseI, and introducing an enzymatic portion of a ribozyme encoding sequence within the fragments generated by said fragmenting by cleaving each said fragment and then ligating said enzymatic portion of a ribozyme encoding sequence into each said fragment.