DELIVERY IS ONE OF THE PRImary hurdles to developing drugs based on the gene-silencing technique called RNA interference (RNAi). Scientists at Alnylam Pharmaceuticals in Kulmbach, Germany, and Cambridge, Mass., now show that chemical modification can assist delivery of the short interfering RNAs (siRNAs) used in RNAi { Nature , 432 ,173 (2004)}. By conjugating the siRNAs to cholesterol, the researchers improved the stability of the siRNAs in blood and mediated their uptake by cells. The scientists demonstrated the method with apolipoprotein B, a protein involved in the formation of low-density lipoproteins (LDLs, the bad cholesterol). They prepared modified siRNAs designed to target the genes for apolipoprotein B. When injected into mice, the cholesterol-conjugated siRNAs were taken up by the liver and other tissues, where they significantly reduced expression of apolipoprotein B, leading to lower levels of blood cholesterol. Don't expect an RNAi therapeutic to hit doctors' offices too quickly, though. ...