Depending on which delivery method is selected, stabilizing RNAi compounds by chemical modification may be critical for RNAi activity in animal models and in humans.  The stabilization may be necessary to protect the RNAi compounds from being degraded by enzymes that exist in bodily fluids.  Many of RXi’s employees and scientific advisory board members are leaders in the design of chemically modified RNAi.  RXi will employ their collective expertise to design chemically modified RNAi compounds.  RXi has in-licensed technology on chemically stabilized RNAi compounds that will also form the basis of its chemical modification strategy.

RXi’s founding scientists recognized very early that the key to therapeutic success with RNAi lies in delivering intact RNAi compounds to the target tissue and the interior of the target cells.  RXi will work with chemically synthesized RNAi compounds that are optimized for stability and efficacy.  RXi intends to rely on a combination of delivery at the site of action and formulation with delivery agents to achieve optimal delivery to specific target tissues. 

One of RXi’s founding scientists, Dr. Tariq Rana, has developed novel and proprietary nanotransporters that have been shown to deliver RNAi compounds to target tissues in animal models. A nanotransporter is a chemical that is mixed with an RNAi compound to form minute particles which transport RNAi compounds to tissues. RXi has an exclusive therapeutic license to Dr. Rana’s technology, which has been used to deliver RNAi compounds to the mouse liver and obtain exceptionally low dose (1 mg/kg) gene specific inhibition.  Delivery to the liver is critical for many diabetes, obesity and other metabolic targets. In addition, Dr. Rana’s nanotransporters are of a defined size and are readily formulated.

Figure - Schematic diagram of a nanotransporter

The nanotransporter is a chemical that is mixed with RNAi compound to form minute particles which transport RNAi to tissues. The nanotransporter has a core to which layers (shown as G1, G2, and G3 in the figure above) are added by chemical synthesis. The final layer has positive charges (shown as Zs in the figure above) which attract and bind to negatively charged RNAi compounds. RXi believes that nanotransporter delivery has the following potential advantages:

• Inhibition of liver target with 1 mg RNAi compound per kg of body weight
• No immune stimulation detected
• Defined particle size
• Readily formulated