RNAi interference has been touted as a potential medical silver bullet since it was discovered in the mid 1990s. Now a study published in Nature reports the successful use of RNAi for medical purposes in primates.

RNAi is induced by small interfering RNA molecules or siRNAs. These bind the messenger RNAs (mRNAs) which serve as the intermediate information carrier between gene and protein. The resulting double helix is targeted for degradation by a specialised enzyme, preventing its translation into protein. siRNAs target specific genes, effectively silencing their expression.

The most exciting aspect of RNAi is the fact that it can spread beyond the point of RNA introduction throughout the entire organism, and in recent years research has started to focus on the use of RNAi as a therapeutic tool (e.g. in the treatment of cancer or of viral infections like HIV).

In this latest paper, scientists constructed siRNAs which would specifically target the mammalian ApoB gene. The ApoB protein is essential for the synthesis of low-density lipoprotein (LDL) which transports cholesterol around the body. High levels of ApoB and LDL are associated with an increased risk of coronary heart disease and other arterial diseases, which can prove fatal. However, ApoB is not a suitable target for conventional drug therapy.

The researchers injected monkeys with ApoB siRNAs and observed a marked and dose-dependent drop in blood ApoB and LDL levels within twenty-four hours of inoculation. Blood cholesterol levels fell by up to 60% after just one treatment with siRNAs. These effects were sustained over several days. Importantly, the animals showed no apparent changes in blood clotting and no immune reaction. This gives hope for the development of an RNAi-based treatment for hypercholesterolaemia in humans. Ian McLachlan, who led the study, said that “ultimately, we feel it might be possible to develop a therapeutic which requires monthly or quarterly injections.” (Quoted in New Scientist).

(Advance online publication of the original article can be found here.