RNA interference, which involves designing molecular 鈥渟mart bombs鈥� to switch off genes, holds vast promise for medicine. The only problem is that while some bombs are spectacular successes, others are dismal failures. But a biotech company says it has now developed a way to make them more effective and screen out the duds.
RNA interference (RNAi) works by triggering an attack on the messenger RNA that spools off a gene, which is then used to make the protein. To make the bombs, researchers create a small RNA molecule that matches part of the sequence of the target gene.
These small interfering RNAs (siRNAs) also occur naturally, as part of a defence system cells use to destroy viral invaders and control gene activity. RNAi has been a boon to geneticists who want to knock out genes to discover their function, and is also being explored as a novel way to treat diseases.
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But although any matching siRNA should work in theory, it doesn鈥檛 happen in practice. Steve Daniel of Dharmacon in Lafayette, Colorado, says the company鈥檚 research team has found that most of the time a randomly chosen siRNA only reduces a gene鈥檚 activity by half or less. For some genes, finding any effective siRNA is a struggle. So Daniel鈥檚 team developed a set of 34 criteria for screening out ineffective sequences.
Using another set of rules, they also found a way to pool two or more siRNAs to launch a coordinated attack on the target sequence. The result is a dramatic increase in effectiveness: 97 per cent of the joint attacks were at least as active as the most effective single siRNA. And 23 per cent were more active. Dharmacon says it now guarantees its siRNA pools will cut a gene鈥檚 activity by 75 per cent.
Daniel says he won鈥檛 give further details about the selection criteria until they have been published. But he confirmed that one step is to screen the entire genome of the target organism for close matches to a siRNA sequence. These might act as decoys for the true target, diffusing the firepower of the siRNA.