RNA InterferenceSilence Therapeutics is engaged in translating innovation into the new medicine harnessing RNA Interference for therapeutic intervention
The discovery of RNA interference (RNAi) is considered one of the most exciting and significant medical breakthroughs of recent years. With the ability to selectively silence any gene in the genome, RNAi not only provides an indispensable research tool for unraveling gene function, but also offers potential for the development of novel therapeutics that silence specific genes involved in disease.
RNAi is a naturally occurring cellular method of gene regulation that is thought to have evolved from an early defense mechanism against viruses. The presence of double stranded RNA (dsRNA) is recognized as 'foreign' and is destroyed together with any single stranded RNA including messenger RNA (mRNA) of the same sequence. Destruction of mRNA results in the post transcriptional inhibition of gene expression and the prevention of protein synthesis. RNAi is a potent and highly selective process that may, in principle, be exploited to silence any gene of interest using synthetic siRNAs. Non-target genes are unaffected, reducing the potential for unwanted side effects.
Knockdown of the nuclear envelope protein LaminB (green) in comparison to control in
cultured human cells through RNAi after AtuRNAi® molecule transfection. LaminB1 is a nuclear protein (green);
RNAi of LaminB1 expression results in reduction of the nuclear protein (right).
SiRNA-induced RNAi has become an established and invaluable tool for investigating the link between gene identity and gene function in biological research environments and has been applied to gene screening, target identification and target validation in drug discovery. Perhaps its greatest potential use, however, lies in the development of a new class of RNAi-based therapeutics able to silence any selected gene influencing the initiation or progression of any disease or disease process - from viral genes, oncogenes and inherited defective genes, to genes contributing to multi-factorial diseases such as cancer, heart disease, diabetes, and degenerative disorders.
Synthetic siRNA may be used to inhibit the protein expression of any disease-related gene by exploiting the naturally occurring RNAi process of gene regulation. The potential power and sensitivity of RNAi therapy lies in its ability to silence targeted genes only. Non-target genes are unaffected, reducing the potential for unwanted side effects. RNAi also has the advantage that it does not require the identification of "druggable" domains on the molecular target or specific target locations at the cell membrane.
In common with conventional therapeutics, siRNA must reach the targeted cells, then it should be be able to penetrate the cell membrane and survive long enough inside the cell in order to exert its effects. These are challenges that have been addressed by Silence Therapeutics' proprietary delivery systems ('AtuPLEX®' and others, such as DACC, DBTC) and modified siRNA molecules ('AtuRNAi®').