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

To: SnowShredder who wrote (291)	6/15/2003 10:29:48 AM
From: tom pope	Respond to of 319

I've learned that just because I've just found it does not mean the news is new, but anyway..... Retroviruses prefer transcriptional units The integration pattern of MLV vehicles has important implications for gene therapy \| By Tudor Toma Retroviral integration was assumed to be a random process, and consequently, retroviruses have been considered safe gene delivery vehicles for use in gene therapy. However, recent reports of leukemia in two of 11 children treated for a rare blood disease with a murine leukemia virus (MLV) –based gene therapy vector questioned the random nature of retroviral integration. In the June 13 Science, Xiaolin Wu and colleagues at the National Institutes of Health show that transcription start regions in the human genome are favored targets for MLV integration (Science, 300:1749-1751, June 13, 2003). Wu et al. mapped 903 MLV and 379 human immunodeficiency virus–1 (HIV-1) integrations in the human genome. They observed that MLV preferred integration near the start of transcriptional units, either upstream or downstream. However, HIV-1 preferred integration anywhere in the transcriptional unit but not upstream of the transcriptional start. "That both viruses favor expressed genes is consistent with preferential integration into opened chromatin. However, their preference for distinct regions within genes suggests that active tethering rather than passive diffusion is at play, governed by virus-specific, preintegration complex (PIC) associated determinants," writes Didier Trono from the University of Geneva in an associated editorial. Links for this article E. Check, "Harmful potential of viral vectors fuels doubts over gene therapy," Nature, 423:573-574, June 5, 2003. [PubMed Abstract] X. Wu, "Transcription start regions in the human genome are favored targets for MLV integration," Science, 300:1749-1751, June 13, 2003. sciencemag.org

To: SnowShredder who wrote (291)	6/9/2004 2:03:08 PM
From: Mike McFarland	Read Replies (1) \| Respond to of 319

Got a question for ya--does anybody know if you can change a clinical trial or do companies have to do a whole new protocol and go right back to square one? The reason I ask, is that a fellow on Yahoo/Tgen, 'nerdseeksblond' has several times brought up one of the asgt abstracts {[760] Dual Therapeutic Utility of Proteasome Modulating Agents for Pharmico- Gene Therapy of the Cystic Fibrosis Airway}. I'm not sure this does anything for Targeted Genetics, because I assume that they would have to go back and do a phase I trial. I guess at least one of the drugs they experimented with is a chemo drug, doxorubicin. The paper to read, as far as I can tell, is J Virol. 2004 Mar;78(6):2863-74. Actually, here is his original post. Which I suppose is a very good question. <redfaced...> I hate to admit it went in one ear and out the other when I first read it. messages.yahoo.com