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  A key challenge in the development of RNAi for use as a drug, is the delivery of RNAi molecules to a particular cell or tissue types involved in disease. The first generation of Nucleonics' eiRNA products is based on a plasmid vector, complexed in proprietary formulations of cationic lipids. The formulation technology incorporates the cationic lipids and DNA plasmid into nanoparticles that provide both a targeting and a stabilizing function to the DNA plasmid vector. Target organ delivery is accomplished by varying the composition of the lipid molecules and the method of preparation of the lipid-plasmid complex. Variables such as specific cell-binding constituents, particle size, and particle shape alter the kinetics and distribution of the lipid-DNA complex within the body.
The liver-targeted eiRNA vectors in the Nucleonics' pipeline are currently formulated for intravenous administration and distribute mainly to liver hepatocytes, which are the primary cells infected by the HBV and HCV viruses. One of the most important refinements of Nucleonics' formulation technology involves striking an appropriate balance between achieving high stability of the lipid complex with an opposing, equally desirable property of the complexes' ability to fuse with cellular membranes and efficiently allow release of the DNA for uptake and subsequent transcription in the cell nucleus. Optimization of these properties is the hallmark of successful tissue targeting.
The diagram below provides a schematic overview of the nanoparticles formed with Nucleonics' formulation technology.
 Nucleonics is also actively testing non-viral DNA vector delivery formulations capable of targeting tissues other than the liver, such as epithelial cells of the lung, macrophages, and tumor tissues, which will be useful for development of eiRNA drugs against several diseases. Nucleonics researchers have been developing in vivo delivery formulations for complexed plasmid DNA utilizing the following routes of drug administration:
Nucleonics has optimized proprietary methods for commercial scale production and purification of plasmid DNA with a special focus on ensuring the stability and fidelity of multitarget RNAi expression vectors. Nucleonics' vectors are unique in that they contain the short inverted repeat elements inherent in RNAi structures, as well as multiple copies of proprietary, optimized Pol III promoters. Nucleonics' proprietary DNA plasmid manufacturing techniques have consistently produced DNA material in commercial yields while also demonstrating the ability to meet the technical requirements for DNA plasmid based human therapeutics that have been established by the WHO and US FDA.
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