IF YOU suffered from high cholesterol and were offered a single injection guaranteed to halve your blood cholesterol within hours, would you accept it? That scenario is a step closer, following a major success with a technique called RNA interference reported this week.
RNAi allows disease-causing genes to be switched off at will by interfering with a cell鈥檚 RNA, giving it huge clinical potential. The difficulty so far has been in finding ways to get RNAi-based therapies into cells.
Now a team led by Ian MacLachlan of the Canadian company Protiva Biotherapeutics in Burnaby, British Columbia, has used RNAi in a cynomolgus monkey to rapidly silence the gene that manufactures low-density lipoprotein (LDL), the 鈥渂ad鈥� cholesterol from the liver that clogs up people鈥檚 arteries and so leads to heart disease. The team found that a single injection into the bloodstream cut activity of the gene by 90 per cent within two days. Total cholesterol levels fell by as much as 62 per cent, and LDL by 82 per cent (Nature, DOI: 10.1038/nature04688).
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鈥淥ne injection into the bloodstream cut total cholesterol levels by 62 per cent, and LDL by 82 per cent鈥�
The benefits lasted the full 11 days until the experiment was halted. 鈥淯ltimately, we feel it might be possible to develop a therapeutic which requires monthly or quarterly injections,鈥� MacLachlan says.
The treatment is a major milestone because the RNAi was injected into the blood. All previous treatments have required the RNAi to be injected at the site where it was supposed to act. 鈥淚t鈥檚 the first systemic treatment in primates,鈥� says MacLachlan, who developed it jointly with Alnylam Pharmaceuticals of Cambridge, Massachusetts.
RNAi blocks a gene鈥檚 output by using so-called small interfering RNAs (siRNAs) which contain a sliver of the gene鈥檚 own sequence written back-to-front. MacLachlan got the siRNAs into liver cells by packaging them inside fatty packages called liposomes specifically designed to infiltrate liver cells.
