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Biotech / Medical : Gene therapy -- Ignore unavailable to you. Want to Upgrade?

To: Mike McFarland who wrote (125)	8/13/1999 1:22:00 PM
From: SnowShredder	Read Replies (4) \| Respond to of 319

Hi Mike, AAV vectors are good in the sense that they have site specific integration (if they can get it to work efficiently, although I haven't checked recently), that would be great for stable long term expression. They main drawback is that their is a packaging size limitation of ~4 Kb of DNA...including the promoter...so if you have a gene that has a longer DNA sequence then what? If the integration is random then why not use lentiviral vectors, as they infect and integrate randomly into both dividing and nondividing cells, and have a packaging size limit of ~10Kb of DNA. But if wild type virus is formed then your bummed, and the titer is too low for efficient in vivo use. Retroviral vectors are reletively safe, randomly integrate, and have a packaging limit of 10 Kb of DNA. Unfortunately, their titer is too low for effective use in vivo and can only infect dividing cells. Liposomes or DNA complexes are nice in that, they don't have a packaging limit, are easy to manipulate, and that they are not pathogenic, but they have transient expression and they are not that efficient in delivery. Adenoviral vectors depending on the type have a packaging limit of ~10Kb for E1/E3 deleted, or ~36 Kb for the helper-dependent form. They have a high enough titer for use <in vivo/i>, but they remain episomal, resulting in transient expression...as well as having creating a immune response, limiting the length of transgene expression (Cytotoxic T-cells attack the transduced cells, especially with E1,E3 deleted vectors, not really a problem with helper-dependent Ad vectors). Just a little vector background...if anyone has anything to add or change, feel free to contribute. Best of Luck, Where'd He Go?

To: Mike McFarland who wrote (125)	9/5/1999 10:36:00 AM
From: Mike McFarland	Read Replies (1) \| Respond to of 319

A review of Ariad--and AAV patents, Avigen First, see the bottom part of this post--where Rick also supplied the link to the Avigen patent. siliconinvestor.com ...now there is no doubt that in a momentum oriented market like this the best performers keep running, while poorly performing stocks have a hard time reversing. CEGE and AVGN have been doing very well of late...while long-suffering holders of ARIA wait for an ARGENT partner. Awhile back there was a subthread going over on the Yahoo Ariad thread regarding vectors and patents-- there was a lot of interest when Avigen sent out press release making broad claims with regards to it's AAV patents. But the issue was partly resolved in my mind with the two posts that begin here: messages.yahoo.com --Thats post 648...and read up through 656 Any thoughts? Sure, the market likes CEGE and AVGN right now, and that may be because folks perceive they have a better position as far as the vector--but maybe this is not so. I still think folks are overlooking a genuine bargain in Ariad (and becoming a better bargain by the day I'm afraid to say). I know that sometimes things are cheap for a reason...I don't want to discuss the dilution anymore...a 20M market cap and 30M total shares with an expected partnership this fall is just too damn cheap, it was cheap at $2, it's a bargain below a buck...as long as a partner and cash are found). Ariad has several things going on: 1. ARGENT for GvH--Fas (I've wondered if any adoptive immunotherapy partnerships might come of this--besides BMT, maybe something a little more targeted for the CTLs?) 2. ARGENT for protein therapy using Genovo vector. 3. A new 'pulsatile' insulin regulation scheme--I have not seen much about this...but see smallcapsonline and the BancBoston report from June to see a few snips on this. 4. Hoecst/Ariad Genomics center Thank goodness I did not load up back in June, for I surely would have been stopped out by now. I'm not happy about having given up my gains from trading to suffer in ARIA...but I do think at this price Ariad warranted a quick review here on the Gene Therapy thread. Also see the post to which this is linked if you're new to the thread. I have a high tolerance for risk, that only lately is being tested.