Benitec Biopharma’s patented gene silencing technology, ddRNAi, has the potential to deliver cure as well as treatment of chronic and life-threatening diseases, due to its long lasting effects. (Read full technology details here.)
The synthetic RNA interference approach (What is RNAi) based on siRNA (small interfering RNA) introduces externally-manufactured dsRNA silencing molecules into a target cell, where they enter a natural RNAi pathway to silence a particular gene.
Because dsRNA is fragile, unless modified, it is difficult to deliver to target cells in target organs without the risk of degradation. Even if successful delivery of intact RNA molecules is achieved, the treatment effect will be transient, lasting hours or maybe days. This means that, for siRNA to be effective, relatively high and repeated doses are needed (Advanced Drug Delivery Reviews 2010). These difficulties may explain why several programs based on siRNA have been discontinued in recent years.
ddRNAi introduces DNA-based constructs directly to the nucleus, so the cell is directed to make its own siRNA (via an shRNA intermediary) to silence the gene of interest. Also, because ddRNAi is based on DNA, a range of well-characterised gene therapy delivery options are available. In addition, because ddRNAi results in a genetic change to the cell’s own DNA (expressing a specific RNAi molecule), the effect is long-lasting, persisting for weeks to years (Sci Trans Med 2010).
This DNA-directed approach also means that as little as a single dose may be needed, so complications resulting from high dosage and repeated administration are minimized. As a result, ddRNAi has significant potential for very long term treatment and possibly cure of a range of human disorders.