Ribozymes with optimized hybridizing arms, stems, and loops, tRNA embedded ribozymes and compositions thereof

摘要

This invention is directed to improved catalytic compounds, hammerhead ribozymes, capable of hybridizing with a target RNA to be cleaved. These improved compounds have optimized stems (X)m*(X)m', loops (X)b and hybridizing arms. The invention is also directed to compositions for enhanced RNA cleavage which comprise a first synthetic non-naturally occurring oligonucleotide compound which comprises nucleotides whose sequence defines a conserved catalytic region and nucleotides whose sequence is capable of hybridizing with a predetermined target sequence and a second synthetic non-naturally occurring oligonucleotide which does not contain the predetermined target sequence and is complementary to at least a portion of the first oligonucleotide compound. The invention is also directed to synthetic non-naturally occurring oligonucleotide compounds embedded in a tRNA. The ribozymes and compositions of the present invention may be used in vitro or in vivo. They may be used as diagnostic or therapeutic agents.