RNAi provides an indispensable research tool for unravelling gene function, and also offers potential for the development of novel therapeutics that silence specific genes involved in disease.
RNAi is a naturally occurring cellular mechanism for gene regulation. The presence of double stranded RNA (dsRNA) in a cell is recognised 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 short interfering RNA (siRNA). Non-target genes are unaffected, reducing the potential for unwanted side effects.
The greatest potential use of siRNA-induced RNAi is in the development of a new class of RNAi-based therapeutics. These could silence any selected gene influencing the initiation or progression of a disease or disease process – from viral genes or inherited defective genes, to genes that contribute to multi-factorial diseases such as cancer, heart disease, diabetes, and degenerative disorders.
Synthetic siRNA may be used to inhibit the expression of any disease-related gene by exploiting the naturally occurring RNAi process. The potential power and sensitivity of RNAi therapeutics lies in its ability to silence targeted genes only.
siRNA must reach the targeted cells and needs to be able to penetrate the cell membrane and survive long enough inside the cell in order to exert its effects. This challenge of exploiting RNAi for therapeutic purposes is addressed by our proprietary lipoplex-based delivery systems AtuPLEX®, DACC, HepaPLEX and our specially modified AtuRNAi® molecules.
Our patented RNA interference platform is known as AtuRNAi®. It is made up of highly potent, chemically stabilised short-interfering RNA (siRNA) molecules which offer greater stability and better tolerability over conventional siRNA molecules.
- structural features for RNAi molecules
- specific design rules for increased potency
- reduced off-target effects of siRNA sequences
The same scale-up process for all AtuRNAi® molecules also allows faster preclinical development and lower costs.
AtuRNAi® has been chemically modified to result in a blunt-ended, chemically stabilised molecule which contains only naturally-occurring RNA. This modification pattern offers advantages over standard siRNA such as stability against nuclease degradation and prevention from innate immune response.
Rather than decreasing gene function, mRNA delivery is an exciting new method of introducing messenger RNA activity into the cell and stimulating it to produce a target protein, in conditions where this is of therapeutic interest, including genetic deficiencies. This way improved gene expression is achieved without having to make permanent changes to the genome, thus avoiding safety concerns.
We have already demonstrated our ability to deliver functional mRNA in vivo and are actively exploring new opportunities in this space.