I haven't read the article yet but would like to comment on some of your Zuzufool's statements:<<Alnylam was clever in recognizing that compounds with bad biodistribution tend to collect in the liver and kidneys, the organs of detoxification, and initially applying the RNAi technology a target (apoB) expressed within the liver can therefore be seen as an advantage.>>They picked apoB because for decades nobody could find a small molecule to inhibit it (and many tried). Also Isis has presented some data using antisense to block apoB (from their Q3 report):In August 2004, Isis reported preliminary data from a Phase 1 trial of ISIS 301012, a second-generation antisense inhibitor of apoB-100, at the 9th Drug Discovery Technology World Congress in Boston. ISIS 301012 produced dose-dependent, rapid and prolonged reductions of its target, apoB-100, in low density lipoprotein (LDL), very low density lipoprotein (VLDL) and total cholesterol levels in normal volunteers with borderline elevated cholesterol. ApoB-100 is the molecular carrier of LDL and VLDL cholesterol, the "bad" cholesterol involved in heart disease. Isis and Alnylam have a collaboration:Isis Pharmaceuticals Forms Strategic Alliance With Alnylam Pharmaceuticals in RNAi TherapeuticsIsis and Alnylam Bring Together Leading RNAi Patent Estates and Expertise to Develop RNAi Therapeutics 3/11/2004 4:05:00 PM<<I am not sure this can be repeated for many more relevant targets.>>I haven't heard anything about the PK of RNAi yet but maybe we get a surprise. Nobody planed to use Viagra the way it's used nowadays.<<Additionally, RNAi technology will almost always be vulnerable to being submarined by a cheaper small molecule drug that inhibits the same target or pathway.>>That statement IMHO is plainly wrong. With this mindset Amgen and Genentech and many other companies wouldn't exist, i.e no protein baseddrugs. Gotta take some risks and try something new.Santa(posted w/o proof-reading, hope it's not too confusing)
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