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Biotech / Medical : Ionis Pharmaceuticals (IONS) -- Ignore unavailable to you. Want to Upgrade?

To: Miljenko Zuanic who wrote (1315)	12/2/1997 12:14:00 AM
From: james	Read Replies (1) \| Respond to of 4676

MZ <Article in Cell is bad example (not adequate axperiments) for determining telomerase activity rule in cancer cells proliferation/grow.> That is the tricky staff. The exp. is reversed, not a direct answer. If it was telomerase knock-in ( over-expression minicing clinical state) instead of knock-out. It will be much more conviencing. But (1). no obvouse physiological mal-function, so the side-effect will the mininial. (2). no-complementary, so inhibition will create a bottle-neck. People in drug R/D love this kind of stuffs. < Antisense may have better chance, at this time???>. Three approaches to TI by RNA (or DNA or related molecules) substitution of the enzyme's essential RNA fragment. RNA-complement like conventional AS. Which one has been worked on? The last one is catalytic inhibition. You know which one I like. Sorry for the bad links. In Recap sesearch for FGF in Alliance (www.recap.com) regards

To: Miljenko Zuanic who wrote (1315)	12/2/1997 2:10:00 PM
From: Joe Wesley	Read Replies (1) \| Respond to of 4676

Miljenko: From Dr. Agrawal: The following are a few of the significant advantages of mixed-backbone oligonucleotides (MBOs) over PS-oligos: Increased in vivo stability: End-modified MBOs have much greater in vivo stability following administration than do PS-oligos, thereby allowing the oligos to be administered less frequently. Oral and colorectal administration: End-modified MBOs remain stable in the gastrointestinal tract and are absorbed in the body following oral admin.. The pct. of oligo absorbed in the body ranges from 20% to 40% of the administered dose, depending on the nature of the end-modified ODN or ORN. Modulation of PK: Centrally-modified MBOs are degraded at a more controlled rate than PS-oligos in vivo and generate metabolites which are eliminated from most tissues. Increase in biological potency: In in vitro cell culture systems, the antisense activity of a PS-oligo sequence depends on several parameters including its affinity, RNase H activity, cellular uptake and stability toward nucleases. In in vivo models, effectiveness of oligos depends on these parameters as well, but more importantly on PK profile, stability and safety. End modified and centrally modified MBOs have a more favorable PK profile which in turn showes a better antisense activity than do PS-oligo in vivo models. Amateur P.S.: Good question about patents. Maybe Isis could put a patent information page on the website.