Silence Therapeutics is the leading RNAi therapeutics company in Europe. The Company has developed novel, proprietary short interfering RNA (“siRNA”) molecules. These molecules provide a number of advantages over conventional siRNA molecules as they show increased stability against nuclease degradation.  In addition, the Company has developed a proprietary systemic delivery system, AtuPLEX. This enables the delivery of siRNA molecules to targeted diseased tissues and cells in the body, whilst increasing their bioavailability and circulation times.

Several of its proprietary AtuRNAi compounds are currently being developed clinically. In July 2007, Silence Therapeutics formed a research and development collaboration with Astra Zeneca to develop AtuRNAi against five specific targets including those in respiratory indications.  In 2006, RTP-801i-14 was sub-licensed to Pfizer through its collaboration partner Quark Pharmaceuticals, Inc. for the treatment of Age-related Macular Degeneration (AMD). This compound entered the clinic for AMD in early 2007.  Silence Therapeutics also has licenced rights to the AtuRNAi structure of the compound AKLi-5 to Quark.  This compound has commenced clinical trials for acute kidney injury in 2007. A third product using Silence's unique and proprietary chemical formulation entered clinical trials for diabetic macular oedema in July 2008.

Silence Therapeutics began the clinical development of its proprietary AtuRNAi therapeutic molecules for systemic cancer indications, such as gastrointestinal and non-small lung cancer, in 2009. 

Intradigm has developed proprietary nanoparticles that combine the active siRNA molecules with Intradigm’s proprietary and novel PolyTran™ biodegradable peptide-based polymers.  PolyTran is a library of L-histidine and L-lysine co-polymers all of which carry a positive charge which combines passively with the negative charge on the siRNA to form spherical PolyTran nanoparticles. PolyTran nanoparticles are being optimised for efficient siRNA delivery, providing the nanoparticles created by Intradigm with the capability to facilitate intracellular delivery of siRNA payload under hysiologically relevant conditions. 

These nanoparticles are considered to have the potential to enable safe systemic delivery to certain tissues in the body. Furthermore, the modular, multi-component nature of Intradigm’s RNAi nanoparticles also allows for a number of key modifications that can further enhance their delivery features and pharmaceutical properties:

• PEGylation – Increases half-life and reduces immunogenicity
• Attachment of targeting moieties – Specific ligand to enhanceuptake by the targeted cell type