Anti-Genes: siRNA, Ribozymes and Antisense

Kevin   J.   Scanlon

Abstract

Scientists have been working on strategies to selectively turn off specific genes in diseased tissues for the past thirty years. In the 1980s, oligodeoxynucleotides (ODNs) with unique chemistries were tested with model systems both in vitro and in vivo with varying degrees of success. In the 1990s, ribozymes with both antisense and catalytic properties were successfully introduced to the field. Ribozymes were shown to selectively knock down targeted genes in human tumors grown in mice but delivery issues for these therapeutic anti-genes limited their clinical utility. Short interfering RNA (siRNA) is currently the fastest growing sector of this anti-gene field for target validation and therapeutic applications. The siRNA field may have an opportunity to impact the clinic faster than antisense and ribozymes if the scientists can overcome the previous anti-gene limitations. Fortuitously, there have been a several developments involving the expansion of our genomic knowledge coupled with the rapid dissemination of disease genes by the digital revolution. This convergence of the knowledge of the human genome with the speed of digital communication will help facilitate swift changes in the detection and treatment of human illnesses. The anti-gene field is positioned to exploit this timely union of two distinct technologies. Anti-gene molecules have an opportunity to become a successful technology in understanding the human genome, as well as, enabling the development of efficacious gene therapy for human diseases in the near future. This review will characterize the advances in this field and address the challenges to the success of for the anti-gene technology.

Keywords: short interfering rna (sirna), antisense, phosphorothioate oligodeoxynucleotide (odn), ribozymes, nonviral vectors, viral vectors, oncogenes, gene therapy