Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

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

To: scaram(o)uche who wrote (7761)	1/17/2003 3:19:12 PM
From: A.J. Mullen	Read Replies (1) \| Respond to of 52153

Rick, Thanks for the response, but surely insertion is also the job of a virus. Isn't that how viruses reproduce, by hijacking the machinery of the nucleus? With naked DNA too, isn't the attraction that once injected into the nucleus it gets taken up into the genome? I can see though, that if retroviruses are inserting the ('payload") gene all over the place, then the chances of havoc are much greater. Sorry to all if I've been worrying at this like a dog at a dry bone. Ashley

To: scaram(o)uche who wrote (7761)	1/17/2003 3:25:52 PM
From: Biomaven	Respond to of 52153

From a letter in this weeks NEJM from the French doctors involved: We interpret these findings as the consequence of the insertional mutagenesis event, a risk that is potentially associated with retrovirally mediated gene transfer and that has previously been considered to be very low in humans.4 For this reason, a thorough reassessment of the potential risk of retrovirally mediated gene therapy is warranted. It is likely that additional factors may have contributed to the adverse event in our patient, including a varicella?zoster virus infection five months before clinically detectable lymphoproliferation, which may have stimulated immune reactivity of the / T-cell clone, or a selective growth advantage conferred by c expression in the transduced cells. Genetic predisposing factors for childhood cancer are also possible, since medulloblastomas have developed in the proband's sister and a first-degree relative. So this might just have been bad luck. Given that these particular patients die pretty quickly without this procedure, I suspect they will resume treatments using retroviruses for this disorder. But clearly this is a warning flag for retrovirus use for other, less fatal, diseases. Peter

To: scaram(o)uche who wrote (7761)	1/17/2003 3:58:28 PM
From: tuck	Read Replies (1) \| Respond to of 52153

Rick, It is my understanding that part of the problem with adenoviruses is that the delivered transgene doesn't last. To address that, one strategy has been to link a transposon to the payload. So the vector itself is OK, but now the transposon can go off into unwanted places with attached payload, and you've got potential for insertion mutations again. i-sis.org.uk Apparently, the mutations can a take a good while before manifesting as a problem. Didn't the second patient develop his leukemia three years after treatment? No biotech can afford a trial that long. They would have to follow phase II patients to PIII and beyond or something. Or am I manifesting foot in mouth disease again? Cheers, Tuck