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

To: Miljenko Zuanic who wrote (1858)	3/29/1998 5:05:00 PM
From: SnowShredder	Read Replies (1) \| Respond to of 4676

Hi Miljenko, According to the book Human Molecular Genetics by Tom Stachan and Andrew P. Read..."Antisense oligonucleotides, even when chemically modified, are not stable indefinitely. One way of ensuring a continuous supply of antisense sequence is a form of expression cloning in which a specially designed antisense gene is transferred into the relevant cells. Such a gene can be engineered simply by constructing a minigene in which an inverted coding sequence is placed downstream of a powerful promoter. The DNA strand that normally serves as the sense strand is now transcribed to give an antisense RNA which can be synthesized repeatedly. If the antisense gene is provided using an integrative vector, long-term production of antisense RNA may be obtained." @ the Keystone Conference on January 10-15, 1998 "Gene Therapy Strategies for Hematopoietic Cells" in Incline Village, NV...Sadhna Joshi et al presented a poster "Anti-HIV-1 Gene Therapy Using Packageable Multimeric Ribozymes". "Monomeric hammerhead ribozymes (Rzs) designed against highly conserved regions within the 5' leader sequence and pro, RT, gag, env and tat coding regions of HIV-1 mRNAs. Of these, Rz(leaders), Rz (env), and Rz (pro) conferred the best protection...A vector expressing the multimeric Rz(env1-9) targeting nine highly conserved sequences within the HIV-1 env coding region was constructed. This vector conferred excellent protection to MT-4 cells for 60 days tested and also conferred protection to PBLs against challenge with laboratory and primary isolates of HIV-1." I hope that this helps. Best of luck, Where'd He Go?

To: Miljenko Zuanic who wrote (1858)	3/30/1998 9:44:00 AM
From: Perry	Respond to of 4676

>> Antisenses (ISIP) , ribozymes (RZYM) and aptamers (NXTR) are chemically modified RNA/DNA fragments. So, they can't be produced by vector transfer and gene expression technology.<< You guys (Miljenko, Where'd He GO) are both correct. If you could have a stable transfection that continuously produced antisense molecules within the cell then the modified antisense that ISIP uses would be, to some extent, unecessary. However long term stable transfections are still unproven? Furthermore DNA analogs like the phosphorothiaotes that ISIP uses, not only increases resistance to nuclease degradation but also stimulates RNase H activity, whereas other DNA antisense analogs for reasons I am unaware do not stimulate RNase H activity and hence have been shown to be less effective. Good Luck, Perry