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Designing antisense to inhibit the renin-angiotensin system

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Abstract

Overactive renin-angiotensin system has been indicated in numerous pathological situations. Current treatment is based on pharmaceutical compounds, which work on the proteins level. Undisputedly helpful, it is not, however, flawless. Some of the drawbacks include adverse effects and non-compliance problem, since in many cases medicine has to be taken at least once a day for a long time. Therefore it seems logical to try a different approach, for instance to correct the disease at the gene expression level, possibly having a choice of shorter or longer-lasting effects. This current review combines results, relevant to the angiotensin system, with the antisense approach, which decreases amount of target protein by interfering at the mRNA level. Dependent on the tool used - oligodeoxynucleotide, plasmid or viral vector, the antisense effect lasts from few days to months.

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References

  1. Wagner RW: Gene inhibition using antisense oligodeoxynucleotides. Nature 372: 333–335, 1994

    Google Scholar 

  2. Crooke ST: Therapeutic applications of oligonucleotides. Annu Rev Pharmacol Toxicol 32: 329–376, 1992

    Google Scholar 

  3. Stein CA, Cheng Y-C: Antisense oligonucleotides: Is the bullet really magical?. Science 261: 1004–1012, 1993

    Google Scholar 

  4. Chiasson BJ, Hooper ML, Murphy PR, Robertson HA: Antisense oligonucleotide eliminates in vivo expression of c-fos in mammalian brain. Eur J Pharmacol 277: 451–453, 1992

    Google Scholar 

  5. Wahlestedt C, Pich EM, Koob GF, Yee F, Heilig M: Modulation of anxiety and neuropeptide Y-Y1 receptors by antisense oligodeoxynucleotides. Science 259: 528–531, 1993

    Google Scholar 

  6. Wahlestedt C, Golanov E, Yamamoto S, Yee F, Ericson H, Yoo H, Inturrisi CE, Reis DJ: Antisense oligonucleotides to NMDA-R1 receptor channel protect cortical neurons from excitotoxicity and reduce focal ischemic infarctions. Nature 363: 260–263, 1993

    Google Scholar 

  7. McCarthy MM, Masters DB, Rimvall K, Schwartz-Giblin S, Pfaff DW: Intracerebral administration of antisense oligodeoxynucleotides to GAD65 and GAD67 mRNAs modulates reproductive behavior in the female rat. Brain Res 636: 209–220, 1994

    Google Scholar 

  8. Phillips MI: Antisense inhibition and adeno-associated viral vector delivery for reducing hypertension. Hypertension 29: 177–187, 1997

    Google Scholar 

  9. Jeunemaitre X, Soubrier F, Kotelevtsev YV, Lifton RP, Williams CS, Charru A, Hunt SC, Hopkins PN, William RR, Lalouel JM, Corvol P: Molecular basis of human hypertension: Role of angiotensinogen. Cell 71: 169–180, 1992

    Google Scholar 

  10. Kim HS, Krege JH, Kluckman KD, Hagaman JR, Hodgin JB, Best CF, Jennette JC, Coffman TM, Maeda N, Smithies O: Genetic control of blood pressure and the angiotensinogen locus. Proc Natl Acad Sci 92: 2735–2739, 1995

    Google Scholar 

  11. Tanimoto K, Sugiyama F, Goto Y, Ishida J, Takimoto E, Yagami K, Fukamizu A, Murakami K: Angiotensinogen-deficient mice with hypotension. J Biol Chem 269: 31334–31337, 1994

    Google Scholar 

  12. Phillips MI, Mann JFE, Haebara H, Hoffman WE, Dietz R, Schelling P, Ganten D: Lowering of hypertension by central saralasin in the absence of plasma renin. Nature 270: 445–447, 1977

    Google Scholar 

  13. Nazarali AJ, Gutkind JS, Correa FM, Saavedra JM: Decreased angiotensin II receptors in subfornical organ of spontaneously hypertensive rats after chronic antihypertensive treatment with enalapril: Am J Hypertens 3: 59–61, 1990

    Google Scholar 

  14. Phillips MI, Kimura B: Brain angiotensin in the developing spontaneously hypertensive rat. J Hypertens 6: 607–612, 1988

    Google Scholar 

  15. Gyurko R, Wielbo D, Phillips MI: Antisense inhibition of AT1 receptor mRNA and angiotensinogen mRNA in the brain of spontaneously hypertensive rats reduces hypertension of neurogenic origin. Reg Pep 49: 167–174, 1993

    Google Scholar 

  16. Simons RW: Naturally occurring antisense RNA control–a brief review. Gene 72: 35–44, 1988

    Google Scholar 

  17. Bennett CF, Condon TP, Grimm S, Chan H, Chiang MY: Inhibition of endothelial cell adhesion molecule expression with antisense oligonucleotides. J Immunol 152: 3530–3540, 1994

    Google Scholar 

  18. Bacon TA, Wickstrom E: Walking along human c-myc mRNA with antisense oligonucleotides: maximum efficacy at the 5′ cap region. Oncogene Res 6: 13–19, 1991

    Google Scholar 

  19. Cowsert LM, Fox MC, Zon G, Mirabelli CK: In vitro evaluation of phosphorothioate oligonucleotides targeted to the E2 mRNA of papillomavirus: Potential treatment for genital warts. Antimicrob Agents Chemother 37: 171–177, 1993

    Google Scholar 

  20. Lima WF, Monia BP, Ecker DJ, Freier SM: Implication of RNA structure on antisense oligonucleotide hybridization kinetics. Biochemistry 31: 12055–12061, 1992

    Google Scholar 

  21. Sczakiel G, Homann K, Rittner K: Computer-aided search for effective antisense RNA target sequences of the human immunodeficiency virus type 1. Antisense Res Dev 3: 45–52, 1993

    Google Scholar 

  22. Jaroszewski JW, Syi JL, Ghosh M, Ghosh K, Cohen JS: Targeting of antisense DNA: comparison of activity of anti-rabbit beta-globin oligodeoxyribonucleoside phosphorothioates with computer predictions of mRNA folding. Antisense Res Dev 3: 339–348, 1993

    Google Scholar 

  23. Campbell JM, Bacon TA, Wickstrom E: Oligodeoxynucleotide phosphorothioate stability in subcellular extracts, culture media, ser and cerebrospinal fluid. J Biochem Biophys Meth 20: 259–267, 1990

    Google Scholar 

  24. Li B, Hughes JA, Phillips MI: Uptake and efflux of intact antisense phosphorthioate deoxyoligonucleotide directed against angiotensin receptors in bovine adrenal cells. Neurochem Int 31: 393–403, 1997

    Google Scholar 

  25. Iversen PL, Zhu S, Meyer A, Zon G: Cellular uptake and subcellular distribution of phosphorothioate oligonucleotides into cultured cells. Antisense Res Dev 2: 211–222, 1992

    Google Scholar 

  26. Loke SL, Stein CA, Zhang XH, Mori K, Nakanishi M, Subasinghe C, Cohen JS, Neckers LM: Characterization of oligonucleotide transport into living cells. PNAS 86: 3474–3478, 1989

    Google Scholar 

  27. Wagner RW, Matteucci MD, Lewis JG, Gutierrez AJ, Moulds C, Froehler BC: Antisense gene inhibition by oligonucleotides containing C-5 propyne pyrimidines. Science 260: 1510–1513, 1993

    Google Scholar 

  28. Iversen PL, Mata J, Tracewell WG, Zon G: Pharmacokinetics of an antisense phosphorothioate oligodeoxynucleotide against rev from human immunodeficiency virus type 1 in the adult male rat following single injections and continuous infusion. Antisense Res Dev 4: 43–52, 1994

    Google Scholar 

  29. Phillips MI, Wielbo D, Gyurko R: Antisense inhibition of hypertension: A new strategy for renin-angiotensin candidate genes. Kidney Int 46: 1554–1556, 1994

    Google Scholar 

  30. Ambuehl P, Gyurko R, Phillips MI: A decrease of angiotensin receptor number in rat brain nuclei by antisense oligonucleotides against the angiotensin AT1A receptor. Reg Pep 59:171–182, 1995

    Google Scholar 

  31. Wielbo D, Sernia C, Gyurko R, Phillips MI: Antisense inhibition of hypertension in the spontaneously hypertensive rat. Hypertension 25: 314–319, 1995

    Google Scholar 

  32. Morishita R, Gibbons GH, Kaneda Y, Ogihara T, Dzau VJ: Pharmacokinetics of antisense oligodeoxyribonucleotides (cyclin B1 and CDC 2 kinase) in the vessel wall in vivo: Enhanced therapeutic utility for restenosis by HVJ-liposome delivery. Gene 149: 13–19, 1994

    Google Scholar 

  33. Colige A, Sokolov BP, Nugent P, Baserge R, Prockop DJ: Use of an antisense oligonucleotide to inhibit expression of a mutated human procollagen gene (COL1A1) in transfected mouse 3T3 cells. Biochemistry 32: 7–11, 1993

    Google Scholar 

  34. Tomita N, Morishita R, Higaki J, Kaneda Y, Mikami H, Ogihara T: In vivo transfer of antisense oligonucleotide against rat angiotensinogen with HVJ-liposome delivery resulted in reduction of blood pressure in SHR. Hypertension 24: 397–402, 1994

    Google Scholar 

  35. Wielbo D, Simon A, Phillips MI, Toffolo S: Inhibition of hypertension by peripheral administration of antisense oligodeoxynucleotides. Hypertension 28: 147–151, 1996

    Google Scholar 

  36. Zelles T, Mohuczy D, Phillips MI: Inhibition of angiotensin receptor (AT1) expression in NG108-15 cells transfected with AT1 receptor antisense in an adeno-associated viral vector. Soc Neurosci 41.18: (abstr) 83, 1996

    Google Scholar 

  37. Mohuczy D, Gelband C, Phillips MI: Antisense inhibition of AT1 receptor in vascular smooth muscle cells using adeno-associated virusbased vector. Hypertension 33(1 Pt 2): 354–359, 1999

    Google Scholar 

  38. Mohuczy D, Tang XP, Kimura B, Phillips MI: Adeno-associated virusbased vector with angiotensinogen cDNA is effective in rat hepatoma cells. FASEB J 13: A484, 398.18, 1999

    Google Scholar 

  39. Tang XP, Mohuczy D, Zhang Y, Kimura B, Galli SM, Phillips MI: Intravenous angiotensinogen antisense in AAV-based vector decreases hypertension. Am J Physiol 277: H2392–H2399, 1999

    Google Scholar 

  40. Mulligan RC: The basic science of gene therapy. Science 260: 926–932, 1993

    Google Scholar 

  41. Iyer SN, Lu D, Katovich MJ, Raizada MK: Chronic control of high blood pressure in spontaneously hypertensive rat by delivery of angiotensin type 1 receptor antisense. PNAS 93: 9960–9965, 1996

    Google Scholar 

  42. Brody SL, Jaffe HA, Eissa NT, Daniel C: Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis. Nat Genet 8: 42–51, 1994

    Google Scholar 

  43. Quantin B, Perricaudet LD, Tajbakhsh S, Mandel JL: Adenovirus as an expression vector in muscle cells in vivo. PNAS 89: 2581–2584, 1992

    Google Scholar 

  44. Le Gal La Salle G, Robert JJ, Berrard S, Ridoux V, Stratford-Perricaudet LD, Perricaudet M, Mallet J: An adenovirus vector for gene transfer into the neurons and glia in the brain. Science 259: 988–990, 1993

    Google Scholar 

  45. Lu D, Yang H, Raizada MK: Attenuation of Ang II actions by adenovirus delivery of AT1 receptor antisense in neurons and SMC. Am J Physiol 274 (2 Pt 2): H719–H727, 1998

    Google Scholar 

  46. Burcin MM, Schiedner G, Kochanek S, Tsai SY, O'Malley BW: Adenovirus-mediated regulable target gene expression in vivo. PNAS 96: 355–360, 1999

    Google Scholar 

  47. Kochanek S, Clemens PR, Mitani K, Chen HH, Chan S, Caskey CT: A new adenoviral vector: Replacement of all viral coding sequences with 28 kb of DNA independently expressing both full-length dystrophin and beta-galactosidase. PNAS 93: 5731–5736, 1996

    Google Scholar 

  48. Muzyczka N, McLaughin S: Use of adeno-associated virus as a mammalian transduction vector. In: Y. Gluzman, S.H. Hughes (eds). Current Communications in Molecular Biology: Viral Vectors. Cold Spring Harbor Laboratory Press, NY, 1988, pp 39–44

    Google Scholar 

  49. Ponnazhagan S, Nallari ML, Srivastava A: Suppression of human alpha-globin gene expression mediated by the recombinant adeno-associated virus 2-based antisense vectors. J Exp Med 179: 733–738, 1994

    Google Scholar 

  50. Chatterjee S, Johnson PR, Wong KK: Dual-target inhibition of HIV-1 in vitro by means of an adeno-associated virus antisense vector. Science 258: 1485–1488, 1992

    Google Scholar 

  51. Muzyczka N: Use of adeno-associated virus as a general transduction vector for mammalian cells. In: Current Topics in Microbiology and Immunology, vol. 158. Springer-Verlag, Berlin, 1992, pp 97–129

    Google Scholar 

  52. Samulski RJ, Zhu X, Xiao X, Brook JD, Housman DE, Epstein N, Hunter LA: Targeted integration of adeno-associated virus (AAV) into human chromosome 19. EMBO J 10: 3941–3950, 1991

    Google Scholar 

  53. Linden RM, Winocour E, Berns KI: The recombination signals for adeno-associated virus site-specific integration. PNAS 93: 7966–7972, 1996

    Google Scholar 

  54. Lebkowski JS, McNally MM, Okarma TB, Lerch B: Adeno-associated virus: A vector system for efficient introduction and integration of DNA into a variety of mammalian cell types. Mol Cell Biol 8: 3988–3996, 1988

    Google Scholar 

  55. Flotte TR, Carter B, Conrad C, Guggino W, Reynolds T, Rosenstein B, Taylor G, Walden S, Wetzel R: A phase I study of an adeno-associated virus-CTFR gene vector in adult CF patients with mild lung disease. Human Gene Therapy. 7: 1145–1159, 1996

    Google Scholar 

  56. Gyurko R, Phillips MI: Antisense expression vector decreases angiotensin receptor binding in NG108-15 cells. Exp Biol: (abstr) 1915, 1995

  57. Gyurko R, Wu P, Sernia C, Meyer E, Phillips MI: Antisense expression vector decreases angiotensinogen synthesis in H-4 hepatoma cells. American Heart Association 48th Annual Council for High Blood Pressure (abstr) 1994

  58. Zolotukhin S, Potter M, Hauswirth WW, Guy J, Muzyczka N: A ‘humanized’ green fluorescent protein cDNA adapted for high-level expression in mammalian cells. J Virol 70: 4646–4654, 1996

    Google Scholar 

  59. Wu P, Du B, Phillips MI, Bui J, Terwilliger EF: Adeno-associated viral vector mediated transgene integration in non-dividing cells. J Virol 72: 5919–5926, 1998

    Google Scholar 

  60. Mohuczy D, Phillips MI: Adeno-associated virus vector as a highly efficient transporter of exogenous DNA into cells. FASEB J 10: A447, 1996

    Google Scholar 

  61. Xiao X, Li J, Samulski RJ: Production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus. J Virol 72: 2224–2232, 1998

    Google Scholar 

  62. Conway J, Rhys C, Zolotukhin I, Zolotukhin S, Muzyczka N, Hayward G, Byrne B: High-titer recombinant adeno-associated virus production utilizing a recombinant herpes simplex virus type 1 vector expressing AAV-2 rep and Cap. Gene Ther 6: 986–993, 1999

    Google Scholar 

  63. Phillips MI, Mohuczy-Dominiak D, Coffey M, Wu P, Galli SM, Zelles T: Prolonged reduction of high blood pressure with an in vivo, nonpathogenic, adeno-associated viral vector delivery of AT1-R mRNA antisense. Hypertension 29: 374–380, 1997

    Google Scholar 

  64. Kimura B, Mohuczy D, Phillips MI: Injection of AT1 receptor antisense in adeno-associated virus (AAV) attenuates hypertension in the spontaneously hypertensive rat (SHR). FASEB J 12: A90, 1998

    Google Scholar 

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Mohuczy, D., Phillips, M.I. Designing antisense to inhibit the renin-angiotensin system. Mol Cell Biochem 212, 145–153 (2000). https://doi.org/10.1023/A:1007192624989

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