Antisense Technology: Applications Part B by Abelson J.N., Simon M.I., Phillips I.M.

By Abelson J.N., Simon M.I., Phillips I.M.

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Gelband, and M. I. Phillips, Hypertension 33, 354 (1999). [3] ANTISENSE D N A DELIVERY FOR PROLONGED EFFECTS 47 Pcmv TR pAAV-GFP 6254 bp sv4o poly(A) P tk TR neoR FIG. 3. Schematic diagram of a recombinant AAV vector containing gfp gene. In the rAAV-GFP vector almost all of the parental wtAAV genome has been deleted, except for the terminal repeats, and replaced with gfp (A. victoria green fluorescent protein gene) driven by a CMV promoter (Pcmv). Also, the neomycin resistance (neo r) gene has been inserted with a thymidine kinase promoter (Ptk).

Plasmid vectors containing the gene of interest have been tested in many in vitro studies. Some of the examples are mentioned below. Taniguchi et al. I used plasmid with insulin c D N A and a glucocorticoidresponsive p r o m o t e r in the 3' region of insulin c D N A in reverse orientation, so that antisense insulin m R N A is produced in response to glucocorticoids. When fibroblasts transfected with this construct were cultured in the presence of dexamethasone, they showed a reduction in proinsulin production.

13C. Wang, L. Chao, and J. Chao, J. Clin. Invest. 95(4), 1710 (1995). [3] ANTISENSE D N A DELIVERY FOR PROLONGED EFFECTS 35 significantly reduced for 6 weeks and reached a maximum of -46 mmHg reduction. 13 They have also shown that iv injection of atrial natriuretic peptide (ANP) gene as naked ANP reduces hypertension in young SHRs (but not in adult SHRs). 14 To treat hypertension by decreasing activity of the renin-angiotensin system we constructed plasmid vector containing angiotensinogen (AGT) cDNA in antisense orientation under the cytomegaloviru~ (CMV) promoter with the green fluorescent protein (GFP) as a reporter gene.

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