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Gene Therapy in Heart Failure: Forthcoming Therapies

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Heart Failure

Part of the book series: Contemporary Cardiology ((CONCARD))

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Abstract

After a decade of preclinical and early phase clinical investigations, gene therapy has emerged as a genuine therapeutic option with the potential to alter the way clinicians manage patients with coronary heart disease (CAD) and with HF. Initially conceived for the treatment of specific inherited monogenic disorders, gene therapy potential has been extended to also include acquired polygenic diseases, such as HF. True that some investigators believe that gene therapy may still be a long time away. Indeed, gene therapy had multiple “initial” successes followed by the realization that much of the enthusiasm for each success has been perhaps premature. Furthermore, much of the early excitement with regard to this approach has been dampened following the death of a young male in one clinical trial. However, as with all discoveries and new fields, problems will arise, and they need to be and likely will be identified and overcome with time. In this chapter, we discuss the current state of gene therapy in cardiac disease, and particular HF, including vehicles for delivery and human clinical trials.

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References

  1. Tan FL, Moravec CS, Li J, Apperson-Hansen C, McCarthy PM, Young JB, Bond M (2002) The gene expression fingerprint of human heart failure. Proc Natl Acad Sci USA 99:11387–11392

    Article  PubMed  CAS  Google Scholar 

  2. Zhu T, Zhou L, Mori S et al (2005) Sustained whole-body functional rescue in congestive heart failure and muscular dystrophy hamsters by systemic gene transfer. Circulation 112:2650–2659

    Article  PubMed  CAS  Google Scholar 

  3. Nabel EG, Plautz G, Boyce FM, Stanley JC, Nabel GJ (1989) Recombinant gene expression in vivo within endothelial cells of the arterial wall. Science 244:1342–1344

    Article  PubMed  CAS  Google Scholar 

  4. Isner JM (2002) Myocardial gene therapy. Nature 415:234–239

    Article  PubMed  CAS  Google Scholar 

  5. Hajjar RJ, del Monte F, Matsui T, Rosenzweig A (2000) Prospects for gene therapy for heart failure. Circ Res 86:616–621

    Article  PubMed  CAS  Google Scholar 

  6. Lawrie A, Brisken AF, Francis SE, Cumberland DC, Crossman DC, Newman CM (2000) Microbubble-enhanced ultrasound for vascular gene delivery. Gene Ther 7:2023–2027

    Article  PubMed  CAS  Google Scholar 

  7. Chen S, Shohet RV, Bekeredjian R, Frenkel P, Grayburn PA (2003) Optimization of ultrasound parameters for cardiac gene delivery of adenoviral or plasmid deoxyribonucleic acid by ultrasound-targeted microbubble destruction. J Am Coll Cardiol 42:301–308

    Article  PubMed  CAS  Google Scholar 

  8. Baumgartner I, Isner JM (2001) Somatic gene therapy in the cardiovascular system. Annu Rev Physiol 63:427–450

    Article  PubMed  CAS  Google Scholar 

  9. Barbato JE, Kibbe MR, Tzeng E (2003) The emerging role of gene therapy in the treatment of cardiovascular diseases. Crit Rev Clin Lab Sci 40:499–545

    PubMed  CAS  Google Scholar 

  10. Williams ML, Koch WJ (2004) Viral-based myocardial gene therapy approaches to alter cardiac function. Annu Rev Physiol 66:49–75

    Article  PubMed  CAS  Google Scholar 

  11. Isner JM, Vale PR, Symes JF, Losordo DW (2001) Assessment of risks associated with cardiovascular gene therapy in human subjects. Circ Res 89:389–400

    Article  PubMed  CAS  Google Scholar 

  12. Pislau S, Janssens SP, Gersh BJ, Simari RD (2002) Defining gene transfer before expecting gene therapy; putting the horse before the cart. Circulation 106:631–636

    Article  CAS  Google Scholar 

  13. Vinge LE, Raake PW, Koch WJ (2008) Gene therapy in heart failure. Circ Res 102:1458–1700

    Article  PubMed  CAS  Google Scholar 

  14. Dzau VJ (2003) Predicting the future of human gene therapy for cardiovascular diseases: what will the management of coronary artery disease be like in 2005 and 2010? Am J Cardiol 92:32N–35N

    Article  PubMed  Google Scholar 

  15. Morishita R, Higaki J, Tomita N, Ogihara T (1998) Application of transcription factor “decoy” strategy as means of gene therapy and study of gene expression in cardiovascular disease. Circ Res 82:1023

    Article  PubMed  CAS  Google Scholar 

  16. Kibbe MR, Billiar TR, Tzeng E (2000) Gene therapy for restenosis. Circ Res 86:829–833

    Article  PubMed  CAS  Google Scholar 

  17. Mann MJ, Whittemore AD, Donaldson MC et al (1999) Ex-vivo gene therapy of human vascular bypass grafts with E2F decoy: the PREVENT single-centre, randomised, controlled trial. Lancet 354:1493–1498

    Article  PubMed  CAS  Google Scholar 

  18. Isner JM, Walsh K, Symes J et al (1996) Arterial gene transfer for therapeutic angiogenesis in patients with peripheral artery disease. Hum Gene Ther 7:959–988

    Article  PubMed  CAS  Google Scholar 

  19. Isner JM, Walsh K, Rosenfield K, Schainfeld R, Asahara T, Hogan K, Pieczek A (1996) Arterial gene therapy for restenosis. Hum Gene Ther 7:989–1011

    Article  PubMed  CAS  Google Scholar 

  20. Isner JM, Pieczek A, Schainfeld R et al (1996) Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb. Lancet 348:370–374

    Article  PubMed  CAS  Google Scholar 

  21. Tabata H, Silver M, Isner JM (1997) Arterial gene transfer of acidic fibroblast growth factor for therapeutic angiogenesis in vivo: critical role of secretion signal in use of naked DNA. Cardiovasc Res 35:470–479

    Article  PubMed  CAS  Google Scholar 

  22. Vincent KA, Shyu KG, Luo Y et al (2000) Angiogenesis is induced in a rabbit model of hindlimb ischemia by naked DNA encoding an HIF-1a/VP16 hybrid transcription factor. Circulation 102:2255–2261

    Article  PubMed  CAS  Google Scholar 

  23. Zhang YC, Bui JD, Shen L, Phillips MI (2000) Antisense inhibition of b (1)-adrenergic receptor mRNA in a single dose produces a profound and prolonged reduction in high blood pressure in spontaneously hypertensive rats. Circulation 101:682–688

    Article  PubMed  CAS  Google Scholar 

  24. Kimura B, Mohuczy D, Tang X, Phillips MI (2001) Attenuation of hypertension and heart hypertrophy by adeno-associated virus delivering angiotensinogen antisense. Hypertension 37:376–380

    Article  PubMed  CAS  Google Scholar 

  25. Agata J, Chao L, Chao J (2002) Kallikrein gene delivery improves cardiac reserve and attenuates remodeling after myocardial infarction. Hypertension 40:653–659

    Article  PubMed  CAS  Google Scholar 

  26. Chao J, Jin L, Lin KF, Chao L (1998) Atrial natriuretic peptide gene delivery attenuates hypertension, cardiac hypertrophy and renal injury in salt-sensitive rats. Hum Gene Ther 9:1429–1438

    Article  PubMed  Google Scholar 

  27. Chao J, Kato K, Zhang JJ, Dobrzynski E, Wang C, Agata J, Chao L (2001) Human adrenomedullin gene delivery protects against cardiovascular remodeling and renal injury. Peptides 22:1731–1737

    Article  PubMed  CAS  Google Scholar 

  28. Lin KF, Chao L, Chao J (1997) Prolonged reduction of high blood pressure with human nitric oxide synthase gene delivery. Hypertension 30:307–313

    Article  PubMed  CAS  Google Scholar 

  29. Nuss HB, Johns DC, Kaab S, Tomaselli GF, Kass D, Lawrence JH, Marban E (1996) Reversal of potassium channel deficiency in cells from failing hearts by adenoviral gene transfer: a prototype for gene therapy for disorders of cardiac excitability and contractility. Gene Ther 3:900–912

    PubMed  CAS  Google Scholar 

  30. Ennis IL, Li RA, Murphy AM, Marban E, Nuss HB (2002) Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility. J Clin Invest 109:393–400

    PubMed  CAS  Google Scholar 

  31. Burton DY, Song C, Fishbein I et al (2003) The incorporation of an ion channel gene mutation associated with the long QT syndrome (Q9E-hMiRP1) in a plasmid vector for site-specific arrhythmia gene therapy: in vitro and in vivo feasibility studies. Hum Gene Ther 14:907–922

    Article  PubMed  CAS  Google Scholar 

  32. Donahue JK, Heldman AW, Fraser H et al (2000) Focal modification of electrical conduction in heart by viral gene transfer. Nat Med 6:1395–1398

    Article  PubMed  CAS  Google Scholar 

  33. Watanabe K, Nakazawa M, Fuse K et al (2001) Protection against autoimmune myocarditis by gene transfer of interleukin-10 by electroporation. Circulation 104:1098–1100

    Article  PubMed  CAS  Google Scholar 

  34. Yokoseki O, Suzuki J, Kitabayashi H et al (2001) Cis Element decoy against nuclear factor-k B attenuates development of experimental autoimmune myocarditis in rats. Circ Res 89:899–906

    Article  PubMed  CAS  Google Scholar 

  35. Melo LG, Agrawal R, Zhang L et al (2002) Gene therapy strategy for long-term myocardial protection using adeno-associated virus-mediated delivery of heme oxygenase gene. Circulation 105:602–607

    Article  PubMed  CAS  Google Scholar 

  36. Abunasra HJ, Smolenski RT, Morrison K et al (2001) Efficacy of adenoviral gene transfer with manganese superoxide dismutase and endothelial nitric oxide synthase in reducing ischemia and reperfusion injury. Eur J Cardiothorac Surg 20:153–158

    Article  PubMed  CAS  Google Scholar 

  37. Jayakumar J, Suzuki K, Sammut IA et al (2001) Heat shock protein 70 gene transfection protects mitochondrial and ventricular function against ischemia-reperfusion injury. Circulation 104: I303–I307

    Article  PubMed  CAS  Google Scholar 

  38. Chatterjee S, Stewart AS, Bish LT et al (2002) Viral gene transfer of the antiapoptotic factor Bcl-2 protects against chronic postischemic heart failure. Circulation 106:I212–I217

    PubMed  Google Scholar 

  39. Champion HC, Bivalacqua TJ, D’Souza FM et al (1999) Gene transfer of endothelial nitric oxide synthase to the lung of the mouse in vivo. Effect on agonist-induced and flow-mediated vascular responses. Circ Res 84:1422–1432

    Article  PubMed  CAS  Google Scholar 

  40. Pozeg ZI, Michelakis ED, McMurtry MS et al (2003) In vivo gene transfer of the O2-sensitive potassium channel Kv1.5 reduces pulmonary hypertension and restores hypoxic pulmonary vasoconstriction in chronically hypoxic rats. Circulation 107:2037–2044

    Article  PubMed  CAS  Google Scholar 

  41. Kalka C, Tehrani H, Laudenberg B, Vale PR, Isner JM, Asahara T, Symes JF (2000) VEGF gene transfer mobilizes endothelial progenitor cells in patients with inoperable coronary disease. Ann Thorac Surg 70:829–834

    Article  PubMed  CAS  Google Scholar 

  42. Kawamoto A, Gwon HC, Iwaguro H et al (2001) Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation 103:634–637

    Article  PubMed  CAS  Google Scholar 

  43. Hajjar RJ, Samulski RJ (2006) Heart failure: a silver bullet to treat heart failure. Gene Ther 13:997

    Article  PubMed  CAS  Google Scholar 

  44. del Monte F, Hajjar RJ (2003) Targeting calcium cycling proteins in heart failure through gene transfer. J Physiol 546:49–61

    Article  PubMed  CAS  Google Scholar 

  45. Kullo I, Simari R, Schwartz R (1999) Vascular gene transfer: from bench to bedside. Arterioscler Thromb Vasc Biol 19:196–207

    Article  PubMed  CAS  Google Scholar 

  46. Kibbe MR, Tzeng E, Gleixner SL et al (2001) Adenovirus-mediated gene transfer of human inducible nitric oxide synthase in porcine vein grafts inhibits intimal hyperplasia. J Vasc Surg 34:156–165

    Article  PubMed  CAS  Google Scholar 

  47. Gascon-Irun M, Sanz-Gonzalez SM, Andres V (2003) Gene therapy antiproliferative strategies against cardiovascular disease. Gene Ther Mol Biol 7:75–89

    Google Scholar 

  48. Baumgartner I, Pieczek A, Manor O, Blair R, Kearney M, Walsh K, Isner JM (1998) Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. Circulation 97:1114–1123

    Article  PubMed  CAS  Google Scholar 

  49. Vale PR, Losordo DW, Milliken CE, Maysky M, Esakof DD, Symes JF, Isner JM (2000) Left ventricular electromechanical mapping to assess efficacy of phVEGF165 gene transfer for therapeutic angiogenesis in chronic myocardial ischemia. Circulation 102:965–974

    Article  PubMed  CAS  Google Scholar 

  50. Fortuin FD, Vale P, Losordo DW et al (2003) One-year follow-up of direct myocardial gene transfer of vascular endothelial growth factor-2 using naked plasmid deoxyribonucleic acid by way of thoracotomy in no-option patients. Am J Cardiol 92:436–439

    Article  PubMed  CAS  Google Scholar 

  51. Grines C, Rubanyi GM, Kleiman NS, Marrott P, Watkins MW (2003) Angiogenic gene therapy with adenovirus 5 fibroblast growth factor-4 (Ad5FGF-4): a new option for the treatment of coronary artery disease. Am J Cardiol 92:24N–31N

    Article  PubMed  CAS  Google Scholar 

  52. Suhara H, Sawa Y, Fukushima N et al (2002) Gene transfer of human prostacyclin synthase into the liver is effective for the treatment of pulmonary hypertension in rats. J Thorac Cardiovasc Surg 123:855–861

    Article  PubMed  CAS  Google Scholar 

  53. Gelband CH, Katovich MJ, Raizada MK (2000) Current perspectives on the use of gene therapy for hypertension. Circ Res 87:1118–1122

    Article  PubMed  CAS  Google Scholar 

  54. Tomita N, Morishita R, Higaki J et al (1995) Transient decrease in high blood pressure by in vivo transfer of antisense oligodeoxynucleotides against rat angiotensinogen. Hypertension 26:131–136

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  56. Reaves PY, Beck CR, Wang HW, Raizada MK, Katovich MJ (2003) Endothelial-independent prevention of high blood pressure in L-NAME-treated rats by angiotensin II type I receptor antisense gene therapy. Exp Physiol 88:467–473

    Article  PubMed  CAS  Google Scholar 

  57. Phillips MI, Tang Y, Schmidt-Ott K, Qian K, Kagiyama S (2002) Vigilant vector: heart-specific promoter in an adeno-associated virus vector for cardioprotection. Hypertension 39:651–655

    Article  PubMed  CAS  Google Scholar 

  58. Shah AS, White DC, Emani S et al (2001) In vivo ventricular gene delivery of a b -adrenergic receptor kinase inhibitor to the failing heart reverses cardiac dysfunction. Circulation 103:1311–1316

    Article  PubMed  CAS  Google Scholar 

  59. Miyamoto MI, del Monte F, Schmidt U 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 

  60. Hirsch JC, Borton AR, Albayya FP, Russell MW, Ohye RG, Metzger JM (2004) Comparative analysis of parvalbumin and SERCA2a cardiac myocyte gene transfer in a large animal model of diastolic dysfunction. Am J Physiol Heart Circ Physiol 86:H2314–H2321

    Article  PubMed  CAS  Google Scholar 

  61. Ly KY, HQ PF et al (2008) Reversal of cardiac dysfunction after long-term expression of SERCA2a by gene transfer in a pre-clinical model of heart failure. J Am Coll Cardiol 51:1112–1119

    Article  PubMed  CAS  Google Scholar 

  62. He H, Meyer M, Martin JL et al (1999) Effects of mutant and antisense RNA of phospholamban on SR Ca(2+)-ATPase activity and cardiac myocyte contractility. Circulation 31:974–980

    Article  Google Scholar 

  63. del Monte F, Harding SE, Dec GW, Gwathmey JK, Hajjar RJ (2002) Targeting phospholamban by gene transfer in human heart failure. Circulation 105:904–907

    Article  PubMed  CAS  Google Scholar 

  64. Dorn GW 2nd, Molkentin JD (2004) Manipulating cardiac contractility in heart failure: data from mice and men. Circulation 109:150–158

    Article  PubMed  Google Scholar 

  65. Minamisawa S, Hoshijima M, Chu G 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 

  66. Haghighi K, Kolokathis F, Pater L et al (2003) Human phospholamban null results in lethal dilated cardiomyopathy revealing a critical difference between mouse and human. J Clin Invest 111:869–876

    PubMed  CAS  Google Scholar 

  67. Hajjar RJ, Zsebo K, Deckelbaum L et al (2008) Design of a phase 1/2 trial of intracoronary administration of AAV1/SERCA2a in patients with heart failure. J Card Fail 14:355–367

    Article  PubMed  CAS  Google Scholar 

  68. Rockman HA, Chien KR, Choi DJ et al (1998) Expression of a b -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 

  69. Vale PR, Losordo DW, Symes JF, Isner JM (1998) Gene therapy for myocardial angiogenesis. Circulation 98:I-322

    Google Scholar 

  70. Losordo DW, Vale PR, Symes JF (1998) Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischaemia. Circulation 98:2800–2804

    Article  PubMed  CAS  Google Scholar 

  71. Laitinen M, Hartikainen J, Hiltunen MO et al (2000) Catheter-mediated vascular endothelial growth factor gene transfer to human coronary arteries after angioplasty. Hum Gene Ther 11:263–270

    Article  PubMed  CAS  Google Scholar 

  72. Rosengart TK, Lee LY, Patel SR, Kligfield PD, Okin PM, Hackett NR, Isom OW, Crystal RG (1999) Six-month assessment of a phase I trial of angiogenic gene therapy for the treatment of coronary artery disease using direct intramyocardial administration of an adenovirus vector expressing the VEGF121 cDNA. Ann Surg 230:466–470

    Article  PubMed  CAS  Google Scholar 

  73. Hammond KH, McKirnan DM (2001) Angiogenic gene therapy for heart disease: a review of animal studies and clinical trials. Cardiovasc Res 49:561–567

    Article  PubMed  CAS  Google Scholar 

  74. Yla-Herttuala S, Martin JF (2000) Cardiovascular gene therapy. Lancet 355:213–222

    Article  PubMed  CAS  Google Scholar 

  75. Grines CL, Watkins MW, Helmer G et al (2002) Angiogenic gene therapy (AGENT) trial in patients with stable angina pectoris. Circulation 105:1291–1297

    Article  PubMed  CAS  Google Scholar 

  76. Kastrup J, Jørgensen E, Rück A et al (2005) Direct intramyocardial plasmid vascular endothelial growth factor-A165 gene therapy in patients with stable severe angina pectoris A randomized double-blind placebo-controlled study: the Euroinject One trial. J Am Coll Cardiol 45:982–988

    Article  PubMed  CAS  Google Scholar 

  77. Stewart DJ, Hilton JD, Arnold JM et al (2006) Angiogenic gene therapy in patients with nonrevascularizable ischemic heart disease: a phase 2 randomized, controlled trial of AdVEGF(121) (AdVEGF121) versus maximum medical treatment. Gene Ther 13:1503–1511

    Article  PubMed  CAS  Google Scholar 

  78. Ratko TA, Cummings JP, Blebea J, Matuszewski KA (2003) Clinical gene therapy for nonmalignant disease. Am J Med 115:560–569

    Article  PubMed  CAS  Google Scholar 

  79. Chen Z, Ge Y, Kang JX (2004) Down-regulation of the M6P/IGF-II receptor increases cell proliferation and reduces apoptosis in neonatal rat cardiac myocytes. BMC Cell Biol 5:1

    Article  Google Scholar 

  80. Tomita N, Morishita R (2004) Antisense oligonucleotides as a powerful molecular strategy for gene therapy in cardiovascular diseases. Curr Pharm Des 10:797–803

    Article  PubMed  CAS  Google Scholar 

  81. Morishita R, Aoki M, Kaneda Y (2001) Decoy oligodeoxynucleotides as novel cardiovascular drugs for cardiovascular disease. Ann N Y Acad Sci 947:294–301

    Article  PubMed  CAS  Google Scholar 

  82. Ehsan A, Mann MJ (2000) Antisense and gene therapy to prevent restenosis. Vasc Med 5:103–114

    PubMed  CAS  Google Scholar 

  83. Arora V, Devi GR, Iversen PL (2004) Neutrally charged phosphorodiamidate morpholino antisense oligomers: uptake, efficacy and pharmacokinetics. Curr Pharm Biotechnol 5:431–439

    Article  PubMed  CAS  Google Scholar 

  84. Summerton J, Weller D (1997) Morpholino antisense oligomers: design, preparation, and properties. Antisense Nucleic Acid Drug Dev 7:187–195

    Article  PubMed  CAS  Google Scholar 

  85. Chen E, Ekker SC (2004) Zebrafish as a genomics research model. Curr Pharm Biotechnol 5:409–413

    Article  PubMed  CAS  Google Scholar 

  86. Heasman J (2002) Morpholino oligos: making sense of antisense? Dev Biol 243:209–214

    Article  PubMed  CAS  Google Scholar 

  87. Small EM, Warkman AS, Wang DZ, Sutherland LB, Olson EN, Krieg PA (2005) Myocardin is sufficient and necessary for cardiac gene expression in Xenopus. Development 132:987–997

    Article  PubMed  CAS  Google Scholar 

  88. Wood AW, Schlueter PJ, Duan C (2005) Targeted knockdown of insulin-like growth factor binding protein-2 disrupts cardiovascular development in zebrafish embryos. Mol Endocrinol 19:1024–1034

    Article  PubMed  CAS  Google Scholar 

  89. Shu X, Cheng K, Patel N, Chen F, Joseph E, Tsai HJ, Chen JN (2003) Na, K-ATPase is essential for embryonic heart development in the zebrafish. Development 130:6165–6173

    Article  PubMed  CAS  Google Scholar 

  90. Peterkin T, Gibson A, Patient R (2003) GATA-6 maintains BMP-4 and Nkx2 expression during cardiomyocyte precursor maturation. EMBO J 22:4260–4273

    Article  PubMed  CAS  Google Scholar 

  91. Chinnery PF, Taylor RW, Diekert K, Lill R, Turnbull DM, Lightowlers RN (1999) Peptide nucleic acid delivery to human mitochondria. Gene Ther 6:1919–1928

    Article  PubMed  CAS  Google Scholar 

  92. Tyler BM, Jansen K, McCormick DJ et al (1999) Peptide nucleic acids targeted to the neurotensin receptor and administered i.p. cross the blood-brain barrier and specifically reduce gene expression. Proc Natl Acad Sci USA 96:7053–7058

    Article  PubMed  CAS  Google Scholar 

  93. An DS, Xie Y, Mao SH, Morizono K, Kung SK, Chen IS (2003) Efficient lentiviral vectors for short hairpin RNA delivery into human cells. Hum Gene Ther 14:1207–1212

    Article  PubMed  CAS  Google Scholar 

  94. Arts GJ, Langemeijer E, Tissingh R et al (2003) Adenoviral vectors expressing siRNAs for discovery and validation of gene function. Genome Res 13:2325–2332

    Article  PubMed  CAS  Google Scholar 

  95. Hurtado C, Ander BP, Maddaford TG, Lukas A, Hryshko LV, Pierce GN (2005) Adenovirally delivered shRNA strongly inhibits Na(+)-Ca(2+) exchanger expression but does not prevent contraction of neonatal cardiomyocytes. J Mol Cell Cardiol 38:647–654

    Article  PubMed  CAS  Google Scholar 

  96. Seth M, Sumbilla C, Mullen SP et al (2004) Sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) gene silencing and remodeling of the Ca2+ signaling mechanism in cardiac myocytes. Proc Natl Acad Sci USA 101:16683–16688

    Article  PubMed  CAS  Google Scholar 

  97. Vazquez J, Correa de Adjounian MF, Sumners C, Gonzalez A, Diez-Freire C, Raizada MK (2005) Selective silencing of angiotensin receptor subtype 1a (AT1aR) by RNA interference. Hypertension 45:115–119

    PubMed  CAS  Google Scholar 

  98. McTiernan CF, Mathier MA, Zhu X et al (2007) Myocarditis following adeno-associated viral expression of human soluble TNF receptor (TNFRII-Fc) in baboon hearts. Gene Therapy 14:1613–1622

    Article  PubMed  CAS  Google Scholar 

  99. Hajjar RJ, Zsebo K (2007) AAV vectors and cardiovascular disease: targeting TNF receptor in the heart: clue to way forward with AAV? Gene Ther 14:1611–1612

    Article  PubMed  CAS  Google Scholar 

  100. Marín-García J, Ananthakrishnan R, Goldenthal MJ, Pierpont ME (2000) Biochemical and molecular basis for mitochondrial cardiomyopathy in neonates and children. J Inherit Metab Dis 23: 625–633

    Article  PubMed  Google Scholar 

  101. Marín-García J, Goldenthal MJ (2002) Understanding the impact of mitochondrial defects in cardiovascular disease: a review. J Card Fail 8:347–361

    Article  PubMed  CAS  Google Scholar 

  102. Beltrami AP, Barlucchi L, Torella D et al (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114:763–776

    Article  PubMed  CAS  Google Scholar 

  103. Isobe M, Kosuge H, Koga N, Futamatsu H, Suzuki J (2004) Gene therapy for heart transplantation-associated acute rejection, ischemia/reperfusion injury and coronary arteriosclerosis. Curr Gene Ther 4:145–152

    Article  PubMed  CAS  Google Scholar 

  104. Hajjar RJ, Samulski RJ (2006) Heart failure: a silver bullet to treat heart failure. Gene Ther 13:997

    Article  PubMed  CAS  Google Scholar 

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Marín-García, J. (2010). Gene Therapy in Heart Failure: Forthcoming Therapies. In: Heart Failure. Contemporary Cardiology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-147-9_21

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