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Myocardial Adenoviral Vector Delivery for Cardiovascular Gene Therapy

  • Protocol
Cardiac Drug Development Guide

Abstract

Cardiovascular disease remains the leading cause of death in industrialized countries and despite major progress in drug development, morbidity and mortality has not significantly changed over the last couple of decades. Today, still more than half a million people are diagnosed with chronic heart failure (HF) each year in the United States (1,2). Interestingly, efforts to reduce risk factors have not yet lead to major reductions in the incidence of cardiovascular disease and HF in particular. However, for some probable high-risk factors, more long-term studies may be required. Nevertheless, new therapeutic strategies are clearly needed to help combat cardiovascular disease and more importantly, HF.

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REFERENCES

  1. American Heart Association. 2002 Heart and Stroke Statistical Update. http://www.americanheart.org.

  2. Cohn, J. N., Bristow, M. R., Chien, K. R., Colucci, W. S., Frazier, O. H., Leinwand, L. A., et al. (1997) Report of the National Heart, Lung, and Blood Institute Special Emphasis Panel on Heart Failure Research. Circulation 95, 766–770.

    PubMed  CAS  Google Scholar 

  3. Isner, J. M. (2002) Myocardial gene therapy. Nature 415, 234–239.

    Article  PubMed  CAS  Google Scholar 

  4. Rockman, H. A., Koch, W. J., and Lefkowitz, R. J. (2002) Seven membrane spanning receptors and heart function. Nature 415, 206–212.

    Article  PubMed  CAS  Google Scholar 

  5. Kay, M. A., Glorioso, J. C., and Naldini, L. (2001) Viral vectors for gene therapy: The art of turning infectious agents into vehicles of therapeutics. Nat. Med. 7, 33–40

    Article  PubMed  CAS  Google Scholar 

  6. Ylä-Herttuala, S. and Martin, J. F. (2000) Cardiovascular gene therapy. Lancet 355, 213–222.

    Article  PubMed  Google Scholar 

  7. Duckers, H. J. and Nabel, E. G. (2000) Prospects for genetic therapy of cardiovascular disease. Med. Clin. North Am. 84, 199–213.

    Article  PubMed  CAS  Google Scholar 

  8. Benihoud, K., Yeh, P., and Perricaudet, M. (1999) Adenovirus vectors for gene delivery. Curr. Opin. Biotechnol. 10, 440–447.

    Article  PubMed  CAS  Google Scholar 

  9. Wattanapitayakul, S. K. and Bauer, J. A. (2000) Recent developments in gene therapy for cardiac disease. Biomed. Pharmacother. 54, 487–504.

    Article  PubMed  CAS  Google Scholar 

  10. Losordo, D. W., Vale, P. R., Symes, J. F., Dunnington, C. H., Esakof, D. D., Maysky, M., et al. (1998) Gene therapy for myocardial angiogenesis: Initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia. Circulation 98, 2800–2804.

    PubMed  CAS  Google Scholar 

  11. Patel, S. R., Lee, L. Y., Mack, C. A., Polce, D. R., El-Sawy, T., Hackett, N. R., et al. (1999) Safety of direct myocardial administration of an adenovirus vector encoding vascular endothelial growth factor 121. Hum. Gene Ther. 10, 1331–1348.

    Article  PubMed  CAS  Google Scholar 

  12. Symes, J. F., Losordo, D. W., Vale, P. R., Lathi, K. G., Esakof, D. D., Mayskiy, M., et al. (1999) Gene therapy with vascular endothelial growth factor for inoperable coronary artery disease. Ann. Thorac. Surg. 68, 830–836.

    Article  PubMed  CAS  Google Scholar 

  13. White, D. C. and Koch, W. J. (2001) Myocardial gene transfer. Curr. Cardiol. Rep. 3, 37–42.

    Article  PubMed  CAS  Google Scholar 

  14. Fromes, Y., Salmon, A., Wang, X., Collin, H., Rouche, A., Hagege, A., et al. (1999) Gene delivery to the myocardium by intrapericardial injection. Gene Ther. 4, 683–688.

    Article  Google Scholar 

  15. March, K. L., Woody, M., Mehdi, K., Zipes, D. P., Brantly, M., and Trapnell, B. C. (1999) Efficient in vivo catheter-based pericardial gene transfer mediated by adenoviral vectors. Clin. Cardiol. 22, I23–I29.

    Article  PubMed  CAS  Google Scholar 

  16. Kypson, A. P., Peppel, K., Akhter, S. A., Lilly, R. E., Glower, D. D., Lefkowitz, R. J., et al. (1998) Ex vivo adenoviral-mediated gene transfer to the transplanted adult rat heart. J. Thoracic Cardiovasc. Surg. 115, 623–630.

    Article  CAS  Google Scholar 

  17. Kypson, A. P., Hendrickson, S. C., Akhter, S. A., Wilson, K., McDonald, P. H., Lilly, R. E., et al. (1999) Adenoviral-mediated gene transfer of the β2-adrenergic receptor to donor hearts enhances cardiac function. Gene Ther. 6, 1298–1304.

    Article  PubMed  CAS  Google Scholar 

  18. Shah, A. S., White, D. C., Tai, O., Hata, J. A., Pippen, A., Kypson, A. P., et al. (2000) Adenovirus-mediated genetic manipulation of the myocardial β-adrenergic signaling system in transplanted hearts. J. Thorac. Cardiovasc. Surg. 120, 581–588.

    Article  PubMed  CAS  Google Scholar 

  19. Hajjar, R. J., Schmidt, U., Matsiu, T., Guerrero, J. L., Lee, K. H., Gwathmey, J. K., et al. (1998) Modulation of ventricular function through gene transfer in vivo. Proc. Natl. Acad. Sci. USA 95, 5251–5256.

    Article  PubMed  CAS  Google Scholar 

  20. Maurice, J. P., Hata, J. A., Shah, A. S., White, D. C., McDonald, P. H., Dolber, P. C., et al. (1999) Enhancement of cardiac function after adenoviral-mediated in vivo intracoronary β2-adrenergic receptor gene delivery. J. Clin. Invest. 104, 21–29.

    Article  PubMed  CAS  Google Scholar 

  21. White, D. C., Hata, J. A., Shah, A. S., Glower, D. D., Lefkowitz, R. J., and Koch, W. J. (2000) Preservation of myocardial β-adrenergic receptor signaling delays the development of heart failure following myocardial infarction. Proc. Natl. Acad. Sci. USA 97, 5428–5433.

    Article  PubMed  CAS  Google Scholar 

  22. Tevaearai, H. T., Eckhart, A. D., Shotwell, K. F., Wilson, K., and Koch, W. J. (2001) Ventricular dysfunction after cardioplegic arrest is improved after myocardial gene transfer of a-adrenergic receptor kinase inhibitor. Circulation 104, 2069–2074.

    Article  PubMed  CAS  Google Scholar 

  23. Davidson, M. J., Jones, J. M., Emani, S. M., Wilson, K. H., Jaggers, J., Koch, W. J., et al. (2001) Cardiac gene delivery with cardiopulmonary bypass. Circulation 104, 131–133.

    PubMed  CAS  Google Scholar 

  24. Shah, A. S., Lilly, R. E., Kypson, A. P., Tai, O., Hata, J. A., Pippen, A., et al. (2000) Intracoronary adenovirus-mediated delivery and overexpression of the β2-adrenergic receptor in the heart: prospects for molecular ventricular assistance. Circulation 101, 408–414.

    PubMed  CAS  Google Scholar 

  25. Shah, A. S., White, D. C., Emani, S., Kypson, A. P., Lilly, R. E., Wilson, K., et al. (2001) In vivo ventricular gene delivery of a β-adrenergic receptor kinase inhibitor to the failing heart reverses cardiac dysfunction. Circulation 103, 1311–1316.

    Article  PubMed  CAS  Google Scholar 

  26. Emani, S. M., Shah, A. S., White, D. C., Glower, D. D., and Koch, W. J. (2001) Right ventricular gene therapy with a beta-adrenergic receptor kinase inhibitor improves survival after pulmonary artery banding. Ann. Thorac. Surg. 72, 1657–1661.

    Article  PubMed  CAS  Google Scholar 

  27. Marks, A. R. (2000) Cardiac intracellular calcium release channels: Role in heart failure. Circ. Res. 87, 8–11.

    PubMed  CAS  Google Scholar 

  28. Houser, S. R., Piacentino, V. III, and Weisser, J. (2000) Abnormalities of calcium cycling in the hypertrophied and failing heart. J. Mol. Cell Cardiol. 32, 1595–1607.

    Article  PubMed  CAS  Google Scholar 

  29. Bers, D. M. (2002) Cardiac excitation-contraction coupling. Nature 415, 198–205.

    Article  PubMed  CAS  Google Scholar 

  30. Giordano, F. J., He, H., McDonough, P., Meyer, M., Sayen, M. R., and Dillmann, W. H. (1997) Adenovirus-mediated gene transfer reconstitutes depressed sarcoplasmic reticulum Ca2+-ATPase levels and shortens prolonged cardiac myocyte Ca2+ transients. Circulation 96, 400–403.

    PubMed  CAS  Google Scholar 

  31. Hajjar, R. J., Kang, J. X., Gwathmey, J. K., and Rosenzweig, A. (1997) Physiological effects of adenoviral gene transfer of sarcoplasmic reticulum calcium ATPase in isolated rat myocytes. Circulation 95, 423–429.

    PubMed  CAS  Google Scholar 

  32. Inesi, G., Lewis, D., Sumbilla, C., Nandi, A., Strock, C., Huff, K. W., et al. (1998) Cell-specific promoter in adenovirus vector for transgenic expression of SERCA1 ATPase in cardiac myocytes. Am. J. Physiol. 274, C645–C653.

    PubMed  CAS  Google Scholar 

  33. Meyer, M., Bluhm, W. F., He, H., Post, S. R., Giordano, F. J., Lew, W. Y., et al. (1999) Phospholamban-to-SERCA2 ratio controls the force-frequency relationship. Am. J. Physiol. 276, H779–H785.

    PubMed  CAS  Google Scholar 

  34. Sumbilla, C., Cavagna, M., Zhong, L., Ma, H., Lewis, D., Farrance, I., et al. (1999) Comparison of SERCA1 and SERCA2a expressed in COS-1 cells and cardiac myocytes. Am. J. Physiol. 277, H2381–H2391.

    PubMed  CAS  Google Scholar 

  35. Miyamoto, M. I., del Monte, F., Schmidt, U., DiSalvo, T. S., Kang, Z. B., Matsui, T., et al. (2000) Adenoviral gene transfer of SERCA2a improves left-ventricular function in aortic-banded rats in transition to heart failure. Proc. Natl. Acad. Sci. USA 97, 793–798.

    Article  PubMed  CAS  Google Scholar 

  36. del Monte, F., Williams, E., Lebeche, D., Schmidt, U., Rosenzweig, A., Gwathmey, J. K., et al. (2001) Improvement in survival and cardiac metabolism after gene transfer of sarcoplasmic reticulum Ca2+-ATPase in a rat model of heart failure. Circulation 104, 1424–1429.

    Article  PubMed  Google Scholar 

  37. Schmidt, U., del Monte, F., Miyamoto, M. I., Matsui, T., Gwathmey, J. K., Rosenzweig, A., et al. (2000) Restoration of diastolic function in senescent rat hearts through adenoviral gene transfer of sarcoplasmic reticulum Ca2+-ATPase. Circulation 101, 790–796.

    PubMed  CAS  Google Scholar 

  38. del Monte, F., Harding, S. E., Schmidt, U., Matsui, T., Kang, Z. B., Dec, G. W., Gwathmey, J. K., Rosenzweig, A., et al. (1999) Restoration of contractile function in isolated cardiomyocytes from failing human hearts by gene transfer of SERCA2a. Circulation 100, 2308–2311.

    Google Scholar 

  39. Luo, W., Grupp, I. L., Harrer, J., Ponniah, S., Grupp, G., Duffy, J. J., et al. (1994) Targeted ablation of the phospholamban gene is associated with markedly enhanced myocardial contractility and loss of beta-agonist stimulation. Circ. Res. 75, 401–409.

    PubMed  CAS  Google Scholar 

  40. Minamisawa, S., Hoshijima, M., Chu, G., Ward, C. A., Frank, K., Gu, Y., et al. (1999) Chronic phospholamban-sarcoplasmic reticulum calcium ATPase interaction is the critical calcium cycling defect in dilated cardiomyopathy. Cell 99, 313–322.

    Article  PubMed  CAS  Google Scholar 

  41. Freeman, K., Lerman, I., Kranias, E. G., Bohlmeyer, T., Bristow, M. R., Lefkowtiz, R. J., et al. (2001) Alterations in cardiac adrenergic signaling and calcium cycling differentially affect the progression of cardiomyopathy. J. Clin. Invest. 107, 967–974.

    Article  PubMed  CAS  Google Scholar 

  42. Hajjar, R. J., Schmidt, U., Kang, J. X., Matsui, T., and Rosenzweig, A. (1997) Adenoviral gene transfer of phospholamban in isolated rat cardiomyocytes. Rescue effects by concomitant gene transfer of sarcoplasmic reticulum Ca2+-ATPase. Circ. Res. 81, 145–153.

    PubMed  CAS  Google Scholar 

  43. Davia, K., Hajjar, R. J., Terracciano, C. M., Kent, N. S., Ranu, H. K., O’Gara, P., et al. (1999) Functional alterations in adult rat myocytes after overexpression of phospholamban with use of adenovirus. Physiol. Genomics 1, 41–50.

    PubMed  CAS  Google Scholar 

  44. He, H., Meyer, M., Martin, J. L., McDonough, P. M., Ho, P., Lou, X., et al. (1999) Effects of mutant and antisense RNA of phospholamban on SR Ca2+-ATPase activity and cardiac myocyte contractility. Circulation 100, 974–980.

    PubMed  CAS  Google Scholar 

  45. Eizema, K., Fechner, H., Bezstarosti, K., Schneider-Rasp, S., van der Laarse, A., Wang, H., et al. (2000) Adenovirus-based phospholamban antisense expression as a novel approach to improve cardiac contractile dysfunction: comparison of a constitutive viral versus an endothelin-1-responsive cardiac promoter. Circulation 101, 2193–2199.

    PubMed  CAS  Google Scholar 

  46. Prestle, J., Janssen, P. M., Janssen, A. P., Zeitz, O., Lehnart, S. E., Bruce, L., et al. (2001) Overexpression of FK506-binding protein FKBP12.6 in cardiomyocytes reduces ryanodine receptor-mediated Ca2+ leak from the sarcoplasmic reticulum and increases contractility. Circ. Res. 88, 188–194.

    PubMed  CAS  Google Scholar 

  47. Schillinger, W., Janssen, P. M., Emami, S., Henderson, S. A., Ross, R. S., Teucher, N., et al. (2000) Impaired contractile performance of cultured rabbit ventricular myocytes after adenoviral gene transfer of Na+-Ca2+ exchanger. Circ. Res. 87, 581–587.

    PubMed  CAS  Google Scholar 

  48. Zhang, X. Q., Song, J., Rothblum, L. I., Lun, M., Wang, X., Ding, F., et al. (2001) Overexpression of Na+/Ca2+ exchanger alters contractility and SR Ca2+ content in adult rat myocytes. Am. J. Physiol. 281, H2079–H2088.

    CAS  Google Scholar 

  49. Bristow, M. R., Minobe, W., Raynolds, M. V., Port, J. D., Rasmussen, R., Ray, P. E., et al. (1993) Reduced β1 receptor messenger RNA abundance in the failing human heart J. Clin. Invest. 92, 2737–2745.

    Article  PubMed  CAS  Google Scholar 

  50. Ungerer, M., Parruti, G., Bohm, M., Puzicha, M., DeBlasi, A., Erdmann, E., et al. (1994) Expression of β-arrestins and β-adrenergic receptor kinases in the failing human heart. Circ. Res. 74, 206–213.

    PubMed  CAS  Google Scholar 

  51. Milano, C. A., Allen, L. F., Rockman, H. A., Dolber, P. C., McMinn, T. R., Chien, K. R., et al. (1994) Enhanced myocardial function in transgenic mice overexpressing the β2-adrenergic receptor. Science 264, 582–586.

    Article  PubMed  CAS  Google Scholar 

  52. Liggett, S. B., Tepe, N. M., Lorenz, J. N., Canning, A. M., Jantz, T. D., Mitarai, S., et al. (2000) Early and delayed consequences of β2-adrenergic receptor overexpression in mouse hearts: Critical role for expression level. Circulation 101, 1707–1714.

    PubMed  CAS  Google Scholar 

  53. Dorn, G. W., Tepe, N. M., Lorenz, J. N., Koch, W. J., and Liggett, S. B. (1999) Low-and high-level transgenic expression of β2-adrenergic receptors differentially affect cardiac hypertrophy and function in Gαq-overexpressing mice. Proc. Natl. Acad. Sci. USA 96, 6400–6405.

    Article  PubMed  CAS  Google Scholar 

  54. Engelhardt, S., Hein, L., Wiesmann, F., and Lohse, M. J. (1999) Progressive hypertrophy and heart failure in β1-adrenergic receptor transgenic mice. Proc. Natl. Acad. Sci. USA 96, 7059–7064.

    Article  PubMed  CAS  Google Scholar 

  55. Drazner, M. H., Peppel, K. C., Dyer, S., Grant, A. O., Koch, W. J., and Lefkowitz, R. J. (1997) Potentiation of β-adrenergic signaling by adenoviral-mediated gene transfer in adult rabbit ventricular myocytes. J. Clin. Invest. 99, 288–296.

    Article  PubMed  CAS  Google Scholar 

  56. Kawahira, Y., Sawa, Y., Nishimura, M., Sakakida, S., Ueda, H., Kaneda, Y., et al. (1999) Gene transfection of β2-adrenergic receptor into the normal rat heart enhances cardiac response to beta-adrenergic agonist. J. Thorac. Cardiovasc. Surg. 118, 446–451.

    Article  PubMed  CAS  Google Scholar 

  57. Akhter, S. A., Skaer, C. A., Kypson, A. P., McDonald, P. H., Peppel, K. C., Glower, D. D., et al. (1997) Restoration of β-adrenergic signaling in failing cardiac ventricular myocytes via adenoviral-mediated gene transfer. Proc. Natl. Acad. Sci. USA 94, 12,100–12,105.

    Article  PubMed  CAS  Google Scholar 

  58. Kawahira, Y., Sawa, Y., Nishimura, M., Sakakida, S., Ueda, H., Kaneda, Y., et al. (1998) In vivo transfer of a β2-adrenergic receptor gene into the pressure-overloaded rat heart enhances cardiac response to β-adrenergic agonist. Circulation 98, II262–II267.

    PubMed  CAS  Google Scholar 

  59. Lefkowitz, R. J., Rockman, H. A., and Koch, W. J. (2000) Catecholamines, cardiac “β” adrenergic receptors and heart failure. Circulation 101, 634–1637.

    Google Scholar 

  60. Koch, W. J., Rockman, H. A., Samama, P., Hamilton, R. A., Bond, R. A. and Milano, C. A., et al. (1995) Cardiac function in mice overexpressing the β-adrenergic receptor kinase or a βARK inhibitor. Science 268, 1350–1353.

    Article  PubMed  CAS  Google Scholar 

  61. Akhter, S. A., Eckhart, A. D., Rockman, H. A., Shotwell, K. F., Lefkowitz, R. J., and Koch, W. J. (1999) In vivo inhibition of elevated myocardial β-adrenergic receptor kinase activity in hybrid transgenic mice restores normal β-adrenergic signaling and function. Circulation 100, 648–653.

    PubMed  CAS  Google Scholar 

  62. Rockman, H. A., Choi, D. J., Akhter, S. A., Jaber, M., Giros, B., and Lefkowitz, R. J. (1998) Control of myocardial contractile function by the level of β-adrenergic receptor kinase 1 in gene-targeted mice. J. Biol. Chem. 273, 18,180–18,184.

    Article  PubMed  CAS  Google Scholar 

  63. Rockman, H. A., Chien, K. R., Choi, D. J., Iaccarino, G., Hunter, J. J., and Ross, J. Jr. (1998) Expression of a β-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice. Proc. Natl. Acad. Sci. USA 95, 7000–7005.

    Article  PubMed  CAS  Google Scholar 

  64. Harding, V. B., Jones, L. R., Lefkowitz, R. J., Koch, W. J., and Rockman, H. A. (2001) Cardiac βARK1 inhibition prolongs survival and augments β blocker therapy in a mouse model of severe heart failure. Proc. Natl. Acad. Sci. USA 98, 5809–5814.

    Article  PubMed  CAS  Google Scholar 

  65. Tevaearai, H. T., Walton, G. B., Keys, J. R., Eckhart, A. D., Shotwell, K. F., and Koch, W. J. (2001) Acute ischemic myocardial dysfunction is attenuated by inhibiting β-adrenergic receptor kinase (βARK1). Circulation 104, II–36.

    Article  Google Scholar 

  66. Roth, D. M., Gao, M. H., Lai, N. C., Drumm, J., Dalton, N., Zhou, J. Y., et al. (1999) Cardiac-directed adenylyl cyclase expression improves heart function in murine cardiomyopahty. Circulation 99, 3099–3102.

    PubMed  CAS  Google Scholar 

  67. Lai, N. C., Roth, D. M., Gao, M. H., Fine, S., Head, B. P., Zhu, J., McKirnan, M. D., et al. (2000) Intracoronary delivery of adenoviruses encoding adenylyl cyclase VI increases left ventricular function and cAMP-generating capacity. Circulation 102, 2396–2401.

    PubMed  CAS  Google Scholar 

  68. Laugwitz, K. L., Ungerer, M., Schoneberg, T., Weig, H. J., Kronsbein, K., Moretti, A., et al. (1999) Adenoviral gene transfer of the human V2 vasopressin receptor improves contractile force of rat cardiomyocytes. Circulation 99, 925–933.

    PubMed  CAS  Google Scholar 

  69. Weig, H, J., Laugwitz, K. L., Moretti, A., Kronsbein, K., Stadele, C., Bruning, S., et al. (2000) Enhanced cardiac contractility after gene transfer of V2 vasopressin receptors In vivo by ultrasound-guided injection or transcoronary delivery. Circulation 101, 1578–1585.

    PubMed  CAS  Google Scholar 

  70. Mack, C. A., Patel, S. R., Schwarz, E. A., Zanzonico, P., Hahn, R. T., Ilercil, A., et al. (1998) Biologic bypass with the use of adenovirus mediated gene transfer of the cDNA for Vascular Endothelial Growth Factor 121 improves myocardial perfusion and function in ischemic porcine heart. J. Thorac. Cardiovasc. Surg. 115, 168–176.

    Article  PubMed  CAS  Google Scholar 

  71. Sayeed-Shah, U., Mann, M. J. Martin, J., Garchev, S., Reimold, S., Laurence, R., et al. (1998) Complete reversal of ischemic wall motion anormalities by combined use of gene therapy with transmyocardial laser revascularization. J. Thorac. Cardiovasc. Surg. 116, 763–769.

    Article  PubMed  CAS  Google Scholar 

  72. Henry, T, D., Annex, B. H., and Azrin, M. A. (1999) Final results of the VIVA trial of rhVEGF for human therapeutic angiogenesis. Circulation 100, I–476.

    Google Scholar 

  73. Kleiman, N. S. and Califf, R. M. (2000) Results from late-breaking clinical trials sessions at ACCIS 2000 and ACC 2000. J. Am. Coll. Cardiol. 36, 310–311.

    Article  PubMed  CAS  Google Scholar 

  74. Freedman, S. B. and Isner, J. M. (2001) Therapeutic angiogenesis for ischemic cardiovscular disease. J. Mol. Cell. Cardiol. 33, 379–393.

    Article  PubMed  CAS  Google Scholar 

  75. Rosengart, T. K., Lee, L. Y., Patel, S. R., Sanborn, T. A., Parikh, M., Bergman, G. W., et al. (1999) Angiogenesis gene therapy: Phase I assessment of direct intramyocardial dministration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant coronary artery disease. Circulation 100, 468–474.

    PubMed  CAS  Google Scholar 

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Tevaearai, H.T., Eckhart, A.D., Koch, W.J. (2003). Myocardial Adenoviral Vector Delivery for Cardiovascular Gene Therapy. In: Pugsley, M.K. (eds) Cardiac Drug Development Guide. Methods in Pharmacology and Toxicology. Humana Press. https://doi.org/10.1385/1-59259-404-2:351

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  • DOI: https://doi.org/10.1385/1-59259-404-2:351

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-097-7

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