Through subsequent experiments exploring the expression of double-stranded RNAs (dsRNA) in mouse tissues and cells using plasmid vectors designed to specifically induce an RNAi effect, Wyeth/Apollon researchers were among the first to observe specific gene silencing in mammalian cells and adult mammals. The critical discovery inherent in these early observations was that by generating dsRNA within the cell from plasmid DNA expression vectors, instead of administering the dsRNAs directly, the non-specific dsRNA-mediated "stress response" was not detectable. Avoiding the dsRNA-mediated "stress-response" was considered a major toxicity hurdle to overcome for the enablement of RNAi based therapeutics.

Nucleonics was founded upon the premise that the large body of technical know-how, regulatory, and clinical experience obtained with plasmid vectors in the DNA vaccine arena could readily be translated into a technology base that would support human therapeutic applications exploiting RNA interference. Nucleonics' proprietary technology within the RNAi field is referred to as "expressed interfering RNA" or ("eiRNA") and it also incorporates proprietary innovations for the pharmacologic delivery of eiRNA based therapeutics.

With the closing of its $49.2 million Series B venture capital financing in early 2004, Nucleonics secured the capital resources needed to expand its team and access the facilities necessary to advance initial eiRNA drug candidates into early clinical testing while also supporting a pipeline of several other preclinical programs.

During 2004 and 2005, Nucleonics' R&D efforts were directed at developing, validating and optimizing proprietary DNA plasmid delivery technologies that achieved clinically relevant delivery to the liver. While developing an intravenous liver delivery formulation for its initial product candidates, the Company also developed eiRNA drug delivery formulations that have demonstrated potential in pre-clinical animal models for use in the following clinical routes of drug administration; intramuscular injection, intratumoral injection, subcutaneous injection and intaperitoneal injection. Access to multiple routes of drug delivery, greatly expands the therapeutic areas that can be pursued utilizing Nucleonics' proprietary eiRNA technology.

Our first product candidate, NUC-B1000, is a hepatitis B antiviral agent unique for its ability to thwart the emergence of drug resistant variants and to directly target the production of all viral proteins within an HBV infected liver cell. Current antiviral therapies generally target only one viral protein to generate a therapeutic benefit. Utilizing the same liver delivery technology employed by NUC-B1000, Nucleonics is also advancing its hepatitis C therapeutic candidate toward preclinical proof-of-concept studies and ultimately an IND filing in 2009. The company is also currently pursuing additional disease indications in its preclinical development portfolio, including prostate cancer, ovarian cancer and pandemic flu.