Technology
Silencing of genes by RNA interference (RNAi) is a natural mechanism that can be triggered in cells by either DNA-directed (dd)RNAi or short interfering (si) RNA.
Any gene can be silenced using this RNAi approach, and therefore any medical condition caused by a specific gene is a candidate for treatment using this technology.
ddRNAi v siRNA technology diagram
ddRNAi process
- A DNA construct is inserted into a cell, where it enters the nucleus and continually expresses a form of double stranded RNA (dsRNA) known as short hairpin RNA (shRNA).
- The shRNA then enters the cytoplasm where it is rapidly cleaved into siRNA by the enzyme Dicer, a specific type of RNAse III, as part of the natural RNAi process.
- The expressed siRNA, which has been designed to have a specific sequence that corresponds to part of the target gene to be silenced, enters the cellular RNAi pathway where it becomes associated with the enzyme complex known as RISC.
- RISC then causes separation of the double stranded siRNAi molecule into two single strands. After one of the single siRNAi strands (known as antisense) binds to the target RNA, the RISC complex cleaves the target RNA. This results in silencing, also known as "knock down", of the target gene responsible for the disease or condition.
siRNA v ddRNAi
In contrast to ddRNAi, which is expressed continuously in the cell, the siRNA approach requires the siRNA to be synthetically manufactured, formulated and then introduced into the cell. This synthetic siRNA has a transient duration in the cell akin to small molecule therapies. In contrast ddRNAi-based silencing is long-lasting, akin to gene therapy, and is therefore ideal for targeting chronic life-threatening diseases such as infectious diseases and cancer. ddRNAi can be used to treat and potentially cure a very wide range of medical conditions.
Snapshot of ddRNAi benefits v siRNAi
- Long term silencing of genes
- Single construct can target multiple genes
- Significantly reduces the likelihood of development of resistance
- Flexible delivery options
- Lower cost of goods and easier manufacturing
Benitec has the predominant patent position in ddRNAi technology.
