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Author: Santa22 Old School Fool Add to my Favorite Fools Ignore this person (you won't see their posts anymore) Number: of 24983  
Subject: Re: RNAi paper from Alnylam in Nature Date: 11/12/2004 1:10 PM
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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 Therapeutics
Isis 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 based
drugs. Gotta take some risks and try something new.

Santa

(posted w/o proof-reading, hope it's not too confusing)
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