Genes therefore "work" essentially by encoding or controlling RNA molecules. Those which encode messenger RNA (mRNA) molecules direct the synthesis of specific proteins and enzymes. Proteins and enzymes are essential in all biological processes such that many, if not all, diseases and pathologies are accompanied by abnormal gene function that results in either abnormal proteins being made, or normal proteins being made either in the wrong cell or at the wrong time. If the disease is caused by an infection (for example, by a virus) the infecting viral genes would be regarded as the primary source of key "abnormal" RNA expressed within the infected cell.

Many diseases could be treated or cured by finding a way to eliminate a specific abnormal RNA molecule made within the diseased or infected cell. The excitement around RNAi technology is largely due to its tremendous potential to do this with a degree of potency that no other RNA-targeting technology has demonstrated so far. In fact, the RNAi mechanism present within animal cells has only been recognized as such since the late 1990's, therefore new therapies based on RNAi are in the early stages of development. Nevertheless, because of certain advantages in direct drug design, RNAi-based drugs should be faster to discover and test than many traditional drugs have been.

The RNAi mechanism works by selectively destroying targeted RNA molecules inside a cell when it detects an unnatural, "double-stranded" form of another copy of that same RNA molecule. An extensive explanation of double-stranded RNA sequences vs. single-stranded RNA sequences and other RNAi features would be beyond the scope of this web page, however, the essence of the process is that when a specific double-stranded RNA molecule is introduced into a cell (for example by injection, or by a common laboratory method known as "transfection") the RNAi mechanism (a complex of several proteins) can seek out the matching single-stranded RNA molecule already present within the cell and enzymatically degrade it such that it can no longer be translated into a protein. Thus, the nature of the RNAi drug is itself an RNA molecule which must be at least partially double-stranded.

Many researchers within the RNAi field have sought to deliver small dsRNA sequences themselves as therapeutics (siRNA). However, such strategies face challenges, with respect to delivery, sustained activity, manufacturing and drug stability which can require chemical modifications to the dsRNA in order to navigate around the inherent molecular instability of RNA molecules and the potential toxicity of delivering dsRNA to cells and tissues. It is widely recognized that the delivery of dsRNA to cells or whole animals triggers an interferon-mediated inflammatory response (stress response) that can limit the effectiveness of treatment and/or pose significant safety risks. In light of these concerns, Nucleonics has elected to pursue an "eiRNA" (expressed interfering RNA) approach to RNAi therapeutics, whereby a plasmid DNA coding for desired dsRNA is delivered to diseased cells enabling the cells to carry out dsRNA production internally thereby invoking the RNAi response against a targeted disease causing gene.

The Company's eiRNA therapeutics can be engineered to target multiple disease genes and/or multiple sites on a target gene for RNAi induced gene silencing. Additionally the Company’s eiRNA plasmids are based on a DNA plasmid architecture that is similar to DNA vaccine plasmids that have prior clinical experience and therefore the Company’s eiRNA product candidates benefit from established and well defined clinical/regulatory requirements for plasmid DNA.

Since its inception in early 2001, Nucleonics has developed a broad intellectual property portfolio that includes both in-licensed and owned patents and patent applications which support the Company's eiRNA technology and drug delivery platforms.