Progress in the development of nucleic acid therapeutics for cancer.

摘要

Many cancers are characterized by abnormal gene expression. Silencing these aberrantly expressed genes could therefore have therapeutic utility and by virtue of specific targeting, prove less toxic than conventional cancer therapies. A number of strategies for inhibiting gene expression have been developed. Some, such as triple helix forming, or decoy transcription factor binding, oligodeoxynucleotides seek to disrupt gene expression at the level of transcription. Others, such as antisense oligonucleotides (ODN) and short interfering RNA (siRNA) molecules attempt to disrupt expression at the level of mRNA translation. In this review, we provide an overview of gene silencing agents and their development for use as cancer therapeutics. We will focus on mRNA targeting methodologies and discuss issues core to the clinical success of these molecules including cellular delivery, and successful targeting. The potential utility of nucleic acid based therapeutics in the clinic will also be addressed.