Standard Review

RNAi as a novel therapeutic platform technology for oncological solutions

Gowhar Shafi¹, Kaiser Jamil¹*, Atya Kapley², Hemant J. Purohit² and Mohana Ch Vamsy¹

¹Department of Genomics, Stem cells and Translational Medicine Indo-American Cancer Institute and Research Centre Road # 14, Banjara Hills, Hyderabad-500034, A.P. India.

²National Environmental Engineering Research Institute, Nehru Marg, Nagpur

*Corresponding author. E-mail: Kaiser.jamil@gmail.com.

Accepted 4 March 2008.

   Abstract

RNA interference (RNAi) is a process in which double-stranded RNA triggers the degradation of a homologous messenger RNA (sharing sequence-specific homology). RNAi has been observed in all eukaryotes, from yeast to mammals. The power and utility of RNAi for specifically silencing the expression of any gene for which sequence is available has driven its incredibly rapid adoption as a tool for reverse genetics in eukaryotic systems. RNAi is remarkably potent i.e., only a few dsRNA molecules per cell (like catalytic reactions) are required to produce effective interference. The long dsRNAs enter a cellular pathway that is commonly referred to as the RNA interference (RNAi) pathway.  RNAi is now recognized to be one of a larger set of sequence-specific cellular responses to RNA, collectively called RNA silencing. These responses have been shown to play a role not only in mRNA and dsRNA stability/degradation, but also in regulation of translation, transcription, chromatin structure, and genome integrity. RNAi has also been invaluable for unveiling critical pathway involved in cancer development, growth and metastasis and has been useful in identifying critical tumor type specific gene targets for cancer therapy. RNAi has been shown to inhibit gene expression and is considered as one of the most important recent discoveries in molecular oncology. It is already a widely used research tool in the analysis of molecular mechanisms for many diseases including cancer and this is because it allows researchers to silence the expression of specific gene targets, much like antisense technology, but with higher specificity and efficacy. Although RNAi is an evolutionarily conserved phenomenon for sequence specific gene silencing in mammalian cells, exogenous short interfering RNA (siRNA) and vector based short hairpin RNA (shRNA) can also invoke RNAi responses. Both are now not only experimental tools for analyzing gene functions but are also expected to be excellent avenues for drug  target discovery and the emerging class of gene medicine for targeting incurable disease such as cancer. The success of therapeutic use of RNAi for cancer relies on the development of safe and efficacious delivery systems that introduce siRNA and shRNA expression vectors into target tumor cells. The present review provides a brief overview of RNAi based approaches for gene silencing as a potential therapy for cancer.

Key words: RNA interference (RNAi), cancer, posttranscriptional gene silencing, siRNA, miRNA.