Preformed ribozyme destroys tumour necrosis factor mRNA in human cells

Maintaining RNA stability is a major problem in the delivery of preformed inhibitory RNA to target cells. In this study, we delivered a hammerhead ribozyme directed against tumour necrosis factor alpha into human promyelocytic leukaemia cells by cationic liposome-mediated transfection. Delivering a ribozyme in this manner reduced by 90% and 85% tumour necrosis factor alpha mRNA and protein, respectively. A modified ribozyme with a bacteriophage T7 transcription terminator at its 3' end was more stable than one lacking this sequence. This indicates that ribozyme stability can be improved by the addition of terminal sequences expected to protect against cellular nucleases.