Ribozymes and siRnas: from structure to preclinical applications

Abstract

The discovery that nucleic acids mediated the inhibition of gene expression in a sequence-specific manner has provided the scientific community with a potentially important tool to analyse gene function and validate drug targets. Selective inhibition of gene expression by ribozymes and small interfering RNAs (siRNAs) is being explored for potential therapeutics against viral infections, inflammatory disorders, haematological diseases and cancer. In order to be used as pharmaceutical drugs, chemical modifications are necessary to increase their stability in vivo. However, such modifications should not affect either the ribozyme cleavage activity or the incorporation of the siRNAs into the RNA interference (RNAi) targeting complex and subsequent mRNA cleavage. To attain stability, ribozymes and siRNAs must also overcome several other problems, including accessibility to target messenger RNAs (mRNAs), efficient delivery to target cells and unwanted non-specific effects.