Multiple gene silencing, at a stroke
simultaneous disabling of multiple genes through its RNA
interference (RNAi) technology.
An Australian company claims to have successfully achieved the simultaneous disabling of multiple genes through RNA interference (RNAi).
Benitec, based in Queensland, used an approach called DNA-directed RNAi (ddRNAi) to knock out messenger RNA and inhibit protein expression. The technology relies on the introduction of a DNA construct into a cell, triggering the production of double-stranded RNA (dsRNA), which is then cleaved into small interfering RNA (siRNA) sequences that destroy the target mRNA.
The company says that its Benitec's ddRNAi technology can be controlled to make the silencing effect transient or permanent. Rival siRNA technologies under development, it maintains, are only capable of transient silencing and are dose dependent, unlike ddRNAi which is catalytic in its effect.
The discovery that the approach can also be used to switch off a number of different genes is a breakthrough, according to Benitec's chief executive John McKinley.
"We believe our 'multiple warhead' capability will allow us to understand more clearly those conditions that result from multiple gene defects -conditions such as Type II diabetes, autoimmune disorders, cardiovascular dysfunctions -- and perhaps also provide viable treatment regimes," he suggested.
The concept of combination therapy, where several drugs attack multiple targets simultaneously, is widely used in the treatment of cancers. Benitec's multi-hit ddRNAi technology could potentially provide a single agent to do the same job and reduce the risk of resistance developing, and can occur, for example, if one drug is given at too low a dose.
ddRNAi sequences can also be used with a range of delivery options not available to the siRNA approach, such as high-efficiency viral vector systems, and are cheaper to produce, according to Benitec.
They can also be used in the form of long constructs, which reduces the need to identify the optimal target site for a given gene and, in conjunction with high throughput shotgun cloning strategies, potentially allows anonymous gene targeting.
