Technology breakthrough

1 December 2014

Silence Therapeutics plc

Messenger RNA technology breakthrough

Silence Therapeutics plc, AIM: SLN ('Silence' or 'the Company'), a leader in the discovery, development and delivery of novel RNA interference (RNAi) therapeutics for the treatment of serious diseases, has made a material addition to its genetic toolkit, confirming the successful production of potentially therapeutic levels of protein in vivo, in pre-clinical animal models, using messenger RNA (mRNA). This approach enables Silence to replace or restore gene expression in pre-clinical animal models, in addition to its existing capability to silence overexpressed genes with its short-interfering RNA (siRNA) platform.

Messenger RNAs are RNA molecules that convey genetic information from DNA in a cell's nucleus to the ribosomes in the cell to specify the type of protein that should be expressed. Current mRNA technology can be used as a vaccine to produce antigens, but the volumes delivered by Silence will potentially enable the treatment of conditions caused by missing genes.

The efficacy of this technology was assessed by delivering different reporter mRNAs that allowed simple quantification of the resulting protein and clear differentiation from endogenous proteins. In these pre-clinical studies, up to a 100,000 fold increase in the circulating protein erythropoietin (EPO) was observed following mRNA delivery to the liver using our improved liposomes, optimised for delivery of larger RNA cargos.

This finding has proven the ability of Silence's technology to deliver potentially therapeutic protein levels that are measurable in the bloodstream. The incorporation of stabilising modifications to the mRNA sequence is currently being investigated in order to achieve a more sustained increase in protein production by the cell's natural machinery.

Separately today, the Company has also announced a trading update and will be hosting a capital markets presentation for investors and analysts.

Ali Mortazavi, Silence's CEO, said:

"The successful delivery of potentially therapeutic levels of mRNA into target cells in pre-clinical animal models is a significant technology breakthrough. We are excited by the speed of progress in this new field as well as its therapeutic potential and expect mRNA therapeutics to become a major component of our pipeline in the future."

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About Silence Therapeutics plc

Silence Therapeutics is a leading RNA interference (RNAi) or 'gene silencing' platform technology company which has proprietary delivery systems. Combined, RNAi and delivery platforms enable the development of multiple products to multiple drug targets allowing the development of novel therapeutics for diseases with high unmet medical need.

Silence is one of a handful of listed companies globally which have human validated RNA delivery technology. Its platform is one of the safest and most widely tested, with over 400 patients dosed and no immune response observed so far. Silence's RNAi platform has been used in three Phase 2 clinical trials, two of which are awaiting results. It also has a robust IP estate protecting its proprietary technology.