Gene therapy for heart disease: Molecular targets, vectors and modes of delivery to myocardium

Expert Review of Cardiovascular Therapy

Volumn 11, Issue 8, 2013, Pages 999-1013

  Scimia, Maria Cecilia ^a   Cannavo, Alessandro ^a   Koch, Walter J ^a  

^a TEMPLE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

clinical trials; delivery methods; gene therapy; gene transfer; heart failure; large animal models; therapeutical targets; translational studies; vectors

Indexed keywords

ADENYLATE CYCLASE; PHOSPHOLAMBAN; PHOSPHOPROTEIN PHOSPHATASE 1; PLASMID DNA; PLASMID VECTOR; PROTEIN DERIVATIVE; SARCOPLASMIC RETICULUM CALCIUM TRANSPORTING ADENOSINE TRIPHOSPHATASE;

DRUG DELIVERY SYSTEM; GENE THERAPY; GENE TRANSFER; HEART DISEASE; HEART FAILURE; HEART MUSCLE; HUMAN; MOLECULARLY TARGETED THERAPY; MUSCLE REGENERATION; NONHUMAN; NONVIRAL GENE THERAPY; REVIEW; VIRAL GENE DELIVERY SYSTEM;

ANIMALS; CLINICAL TRIALS AS TOPIC; GENE TARGETING; GENE TRANSFER TECHNIQUES; GENETIC THERAPY; GENETIC VECTORS; HEART DISEASES; HUMANS; MYOCARDIUM;

EID: 84886768472     PISSN: 14779072     EISSN: 17448344     Source Type: Journal    
DOI: 10.1586/14779072.2013.818813     Document Type: Review

References (155)

1. Lederberg J. Molecular biology, eugenics and euphenics. Nature 198, 428-429 (1963
2. Culver KW, Osborne WR, Miller AD et al. Correction of ADA deficiency in human T lymphocytes using retroviral-mediated gene transfer. Transplant. Proc. 23, 170-171 (1991
3. Hacein-Bey-Abina S, Garrigue A, Wang GP et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J. Clin. Invest. 118, 3132-3142 (2008
4. Ginn SL, Alexander IE, Edelstein ML, Abedi MR, Wixon J. Gene therapy clinical trials worldwide to 2012 - An update. J. Gene. Med. 15, 65-77 (2013
5. Kukua K, Chojnowska L, D a̧browski M et al. Intramyocardial plasmid-encoding human vascular endothelial growth factor A165/basic fibroblast growth factor therapy using percutaneous transcatheter approach in patients with refractory coronary artery disease (VIF-CAD). Am. Heart J. 161, 581-589 (2011
6. Stewart DJ, Kutryk MJ, Fitchett D et al. VEGF gene therapy fails to improve perfusion of ischemic myocardium in patients with advanced coronary disease: Results of the NORTHERN trial. Mol. Ther. 17, 1109-1115 (2009
7. Yang ZJ, Zhang YR, Chen B et al. Phase I clinical trial on intracoronary administration of Ad-hHGF treating severe coronary artery disease. Mol. Biol. Rep. 36, 1323-1329 (2009
8. Fuchs S, Dib N, Cohen BM et al. A randomized, double-blind, placebo-controlled, multicenter, pilot study of the safety and feasibility of catheter-based intramyocardial injection of AdVEGF121 in patients with refractory advanced coronary artery disease. Catheter Cardiovasc. Interv. 68, 372-378 (2006
9. Ripa RS, Wang Y, Jørgensen E, Johnsen HE, Hesse B, Kastrup J. Intramyocardial injection of vascular endothelial growth factor-A165 plasmid followed by granulocyte- colony stimulating factor to induce angiogenesis in patients with severe chronic ischaemic heart disease. Eur. Heart J. 27, 1785-1792 (2006
10. Fortuin FD, Vale P, Losordo DW et al. 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 (2003
11. Hedman M, Hartikainen J, Syvänne M et al. Safety and feasibility of catheter-based local intracoronary vascular endothelial growth factor gene transfer in the prevention of postangioplasty and in-stent restenosis and in the treatment of chronic myocardial ischemia: Phase II results of the Kuopio Angiogenesis Trial (KAT). Circulation 107, 2677-2683 (2003
12. Vale PR, Losordo DW, Milliken CE et al. Randomized, single-blind, placebo-controlled pilot study of catheter-based myocardial gene transfer for therapeutic angiogenesis using left ventricular electromechanical mapping in patients with chronic myocardial ischemia. Circulation 103, 2138-2143 (2001
13. Jessup M, Greenberg B, Mancini D et al. Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): A Phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure. Circulation 124, 304-313 (2011
14. Jaski BE, Jessup ML, Mancini DM et al. Calcium upregulation by percutaneous administration of gene therapy in cardiac disease (CUPID Trial), a first-in-human phase 1/2 clinical trial. J. Card. Fail. 15, 171-181 (2009
15. Zhang SL, Yang ZJ, Zhang YR et al. [Effect of intracoronary adenovirus vector encoding hepatocyte growth factor gene on hematopoietic stem cells mobilization in patients with extensive coronary heart disease]. Zhonghua Xin Xue Guan Bing Za Zhi 35, 504-508 (2007
16. von der Leyen HE, Mügge A, Hanefeld C et al. A prospective, single-blind, multicenter, dose escalation study of intracoronary iNOS lipoplex (CAR-MP583) gene therapy for the prevention of restenosis in patients with de novo or restenotic coronary artery lesion (REGENT I extension). Hum. Gene Ther. 22, 951-958 (2011
17. Alexander JH, Hafley G, Harrington RA et al. Efficacy and safety of edifoligide, an E2F transcription factor decoy, for prevention of vein graft failure following coronary artery bypass graft surgery: PREVENT IV: A randomized controlled trial. JAMA 294, 2446-2454 (2005
18. Raper SE, Grossman M, Rader DJ et al. Safety and feasibility of liver-directed ex vivo gene therapy for homozygous familial hypercholesterolemia. Ann. Surg. 223, 116-126 (1996
19. Roger VL, Go AS, Lloyd-Jones DM et al. Executive summary: Heart disease and stroke statistics - 2012 update: A report from the American Heart Association. Circulation 125, 188-197 (2012
20. Duan D. Challenges and opportunities in dystrophin-deficient cardiomyopathy gene therapy. Hum. Mol. Genet. 15, R253-R261 (2006
21. Watanabe Y, Ito T, Shiomi M. The effect of selective breeding on the development of coronary atherosclerosis in WHHL rabbits. An animal model for familial hypercholesterolemia. Atherosclerosis 56, 71-79 (1985
22. Scanu AM, Khalil A, Neven L et al. Genetically determined hypercholesterolemia in a rhesus monkey family due to a deficiency of the LDL receptor. J. Lipid Res. 29, 1671-1681 (1988
23. Davidson MH, Dillon MA, Gordon B et al. Colesevelam hydrochloride (cholestagel): A new, potent bile acid sequestrant associated with a low incidence of gastrointestinal side effects. Arch. Intern. Med. 159, 1893-1900 (1999
24. Ishibashi S, Goldstein JL, Brown MS, Herz J, Burns DK. Massive xanthomatosis and atherosclerosis in cholesterol-fed low density lipoprotein receptor-negative mice. J. Clin. Invest. 93, 1885-1893 (1994
25. Shichiri M, Tanaka A, Hirata Y. Intravenous gene therapy for familial hypercholesterolemia using ligand-facilitated transfer of a liposome:LDL receptor gene complex. Gene. Ther. 10, 827-831 (2003
26. Zachary I, Morgan RD. Therapeutic angiogenesis for cardiovascular disease: Biological context, challenges, prospects. Heart 97, 181-189 (2011
27. Vera Janavel GL, De Lorenzi A, Cortés C et al. Effect of vascular endothelial growth factor gene transfer on infarct size, left ventricular function and myocardial perfusion in sheep after 2 months of coronary artery occlusion. J. Gene. Med. 14, 279-287 (2012
28. Laguens R, Cabeza Meckert P, Vera Janavel G et al. Entrance in mitosis of adult cardiomyocytes in ischemic pig hearts after plasmid-mediated rhVEGF165 gene transfer. Gene. Ther. 9, 1676-1681 (2002
29. Lazarous DF, Shou M, Stiber JA et al. Adenoviral-mediated gene transfer induces sustained pericardial VEGF expression in dogs: Effect on myocardial angiogenesis. Cardiovasc. Res. 44, 294-302 (1999
30. Furlani AP, Kalil RA, Castro I et al. Effects of therapeutic angiogenesis with plasmid VEGF165 on ventricular function in a canine model of chronic myocardial infarction. Rev. Bras. Cir. Cardiovasc. 24, 143-149 (2009
31. Tio RA, Tkebuchava T, Scheuermann TH et al. Intramyocardial gene therapy with naked DNA encoding vascular endothelial growth factor improves collateral flow to ischemic myocardium. Hum. Gene Ther. 10, 2953-2960 (1999
32. Radke PW, Heinl-Green A, Frass OM et al. Effects of intramyocardial pVEGF165 delivery on regional myocardial blood flow: Evidence for a spatial 'delivery-efficacy' mismatch. Gene. Ther. 11, 1249-1255 (2004
33. Choi JS, Kim KB, Han W et al. Efficacy of therapeutic angiogenesis by intramyocardial injection of pCK-VEGF165 in pigs. Ann. Thorac. Surg. 82, 679-686 (2006
34. Vera Janavel G, Crottogini A, Cabeza Meckert P et al. Plasmid-mediated VEGF gene transfer induces cardiomyogenesis and reduces myocardial infarct size in sheep. Gene. Ther. 13, 1133-1142 (2006
35. Heilmann C, von Samson P, Schlegel K et al. Comparison of protein with DNA therapy for chronic myocardial ischemia using fibroblast growth factor-2. Eur. J. Cardiothorac. Surg. 22, 957-964 (2002
36. Heilmann CA, Attmann T, Thiem A, Haffner E, Beyersdorf F, Lutter G. Gene therapy in cardiac surgery: Intramyocardial injection of naked plasmid DNA for chronic myocardial ischemia. Eur. J. Cardiothorac. Surg. 24, 785-793 (2003
37. Giordano FJ, Ping P, McKirnan MD et al. Intracoronary gene transfer of fibroblast growth factor-5 increases blood flow and contractile function in an ischemic region of the heart. Nat. Med. 2, 534-539 (1996
38. Suzuki G, Lee TC, Fallavollita JA, Canty JM. Adenoviral gene transfer of FGF-5 to hibernating myocardium improves function and stimulates myocytes to hypertrophy and reenter the cell cycle. Circ. Res. 96, 767-775 (2005
39. Ahmet I, Sawa Y, Yamaguchi T, Matsuda H. Gene transfer of hepatocyte growth factor improves angiogenesis and function of chronic ischemic myocardium in canine heart. Ann. Thorac. Surg. 75, 1283-1287 (2003
40. Rastogi S, Guerrero M, Wang M et al. Myocardial transfection with naked DNA plasmid encoding hepatocyte growth factor prevents the progression of heart failure in dogs. Am. J. Physiol. Heart Circ. Physiol. 300, H1501-H1509 (2011
41. Azuma J, Taniyama Y, Takeya Y et al. Angiogenic and antifibrotic actions of hepatocyte growth factor improve cardiac dysfunction in porcine ischemic cardiomyopathy. Gene. Ther. 13, 1206-1213 (2006
42. Yang ZJ, Chen B, Sheng Z et al. Improvement of heart function in postinfarct heart failure swine models after hepatocyte growth factor gene transfer: Comparison of low-, medium- And high-dose groups. Mol. Biol. Rep. 37, 2075-2081 (2010
43. Penn MS, Mendelsohn FO, Schaer GL et al. An open-label dose escalation study to evaluate the safety of administration of nonviral stromal cell-derived factor-1 plasmid to treat symptomatic ischemic heart failure. Circ. Res. 112, 816-825 (2013
44. Kawase Y, Hajjar RJ. The cardiac sarcoplasmic/endoplasmic reticulum calcium ATPase: A potent target for cardiovascular diseases. Nat. Clin. Pract. Cardiovasc. Med. 5, 554-565 (2008
45. Byrne MJ, Power JM, Preovolos A, Mariani JA, Hajjar RJ, Kaye DM. Recirculating cardiac delivery of AAV2/1SERCA2a improves myocardial function in an experimental model of heart failure in large animals. Gene. Ther. 15, 1550-1557 (2008
46. Mariani JA, Smolic A, Preovolos A, Byrne MJ, Power JM, Kaye DM. Augmentation of left ventricular mechanics by recirculation- mediated AAV2/1-SERCA2a gene delivery in experimental heart failure. Eur. J. Heart Fail. 13, 247-253 (2011
47. Mi YF, Li XY, Tang LJ, Lu XC, Fu ZQ, Ye WH. Improvement in cardiac function after sarcoplasmic reticulum Ca2+-ATPase gene transfer in a beagle heart failure model. Chin. Med. J. 122, 1423-1428 (2009
48. Xin W, Li X, Lu X, Niu K, Cai J. Improved cardiac function after sarcoplasmic reticulum Ca(2+)-ATPase gene transfer in a heart failure model induced by chronic myocardial ischaemia. Acta. Cardiol. 66, 57-64 (2011
49. Beeri R, Chaput M, Guerrero JL et al. Gene delivery of sarcoplasmic reticulum calcium ATPase inhibits ventricular remodeling in ischemic mitral regurgitation. Circ. Heart Fail 3, 627-634 (2010
50. Pathak A, del Monte F, Zhao W et al. Enhancement of cardiac function and suppression of heart failure progression by inhibition of protein phosphatase 1. Circ. Res. 96, 756-766 (2005
51. Carr AN, Schmidt AG, Suzuki Y et al. Type 1 phosphatase, a negative regulator of cardiac function. Mol. Cell. Biol. 22, 4124-4135 (2002
52. Braz JC, Gregory K, Pathak A et al. PKC-Alpha regulates cardiac contractility and propensity toward heart failure. Nat. Med. 10, 248-254 (2004
53. Fish KM, Ladage D, Kawase Y et al. AAV9.I-1c delivered via direct coronary infusion in a porcine model of heart failure improves contractility and mitigates adverse remodeling. Circ. Heart Fail. 6, 310-317 (2013
54. Most P, Remppis A, Pleger ST, Katus HA, Koch WJ. S100A1: A novel inotropic regulator of cardiac performance. Transition from molecular physiology to pathophysiological relevance. Am. J. Physiol. Regul. Integr. Comp. Physiol. 293, R568-R577 (2007
55. Most P, Pleger ST, Völkers M et al. Cardiac adenoviral S100A1 gene delivery rescues failing myocardium. J. Clin. Invest. 114, 1550-1563 (2004
56. Pleger ST, Most P, Boucher M et al. Stable myocardial-specific AAV6-S100A1 gene therapy results in chronic functional heart failure rescue. Circulation 115, 2506-2515 (2007
57. Pleger ST. Cardiac AAV9-S100A1 gene therapy rescues post-ischemic heart failure in a preclinical large animal model. Sci. Transl. Med. 3, 92ra64 (2011
58. Minamisawa S, Hoshijima M, Chu G et al. Chronic phospholamban- sarcoplasmic reticulum calcium ATPase interaction is the critical calcium cycling defect in dilated cardiomyopathy. Cell 99, 313-322 (1999
59. MacLennan DH, Kranias EG. Phospholamban: A crucial regulator of cardiac contractility. Nat. Rev. Mol. Cell Biol. 4, 566-577 (2003
60. Pattison JS, Waggoner JR, James J et al. Phospholamban overexpression in transgenic rabbits. Transgenic. Res. 17, 157-170 (2008
61. Hoshijima M, Ikeda Y, Iwanaga Y et al. Chronic suppression of heart-failure progression by a pseudophosphorylated mutant of phospholamban via in vivo cardiac rAAV gene delivery. Nat. Med. 8, 864-871 (2002
62. Iwanaga Y, Hoshijima M, Gu Y et al. Chronic phospholamban inhibition prevents progressive cardiac dysfunction and pathological remodeling after infarction in rats. J. Clin. Invest. 113, 727-736 (2004
63. Eizema K, Fechner H, Bezstarosti K et al. 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 (2000
64. Kaye DM, Preovolos A, Marshall T et al. Percutaneous cardiac recirculation-mediated gene transfer of an inhibitory phospholamban peptide reverses advanced heart failure in large animals. J. Am. Coll. Cardiol. 50, 253-260 (2007
65. Suckau L, Fechner H, Chemaly E et al. Long-term cardiac-targeted RNA interference for the treatment of heart failure restores cardiac function and reduces pathological hypertrophy. Circulation 119, 1241-1252 (2009
66. Hirsch JC, Borton AR, Albayya FP, Russell MW, Ohye RG, Metzger JM. Comparative analysis of parvalbumin and SERCA2a cardiac myocyte gene transfer in a large animal model of diastolic dysfunction. Am. J. Physiol. Heart Circ. Physiol. 286, H2314-H2321 (2004
67. Schoenman ER, Chiaro JA, Jones A, Bastin LD, Coughlin DJ. A comparative analysis of parvalbumin expression in pinfish (Lagodon rhomboides) and toadfish (Opsanus sp.). Comp. Biochem. Physiol. Part A Mol. Integr. Physiol. 155, 91-99 (2010
68. Coutu P, Bennett CN, Favre EG, Day SM, Metzger JM. Parvalbumin corrects slowed relaxation in adult cardiac myocytes expressing hypertrophic cardiomyopathylinked alpha-tropomyosin mutations. Circ. Res. 94, 1235-1241 (2004
69. Wahr PA, Michele DE, Metzger JM. Parvalbumin gene transfer corrects diastolic dysfunction in diseased cardiac myocytes. Proc. Natl Acad. Sci. USA 96, 11982-11985 (1999
70. Day SM, Coutu P, Wang W et al. Cardiac-directed parvalbumin transgene expression in mice shows marked heart rate dependence of delayed Ca2+ buffering action. Physiol. Genomics 33, 312-322 (2008
71. Wang W, Barnabei MS, Asp ML et al. Noncanonical EF-hand motif strategically delays Ca2+ buffering to enhance cardiac performance. Nat. Med. 19, 305-312 (2013
72. Mogensen J, Kubo T, Duque M et al. Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations. J. Clin. Invest. 111, 209-216 (2003
73. Davis J, Wen H, Edwards T, Metzger JM. Thin filament disinhibition by restrictive cardiomyopathy mutant R193H troponin I induces Ca2+-independent mechanical tone and acute myocyte remodeling. Circ. Res. 100, 1494-1502 (2007
74. Nagueh SF, Bachinski LL, Meyer D et al. Tissue Doppler imaging consistently detects myocardial abnormalities in patients with hypertrophic cardiomyopathy and provides a novel means for an early diagnosis before and independently of hypertrophy. Circulation 104, 128-130 (2001
75. Reddy V, Korcarz C, Weinert L, Al-Sadir J, Spencer KT, Lang RM. Apical hypertrophic cardiomyopathy. Circulation 98, 2354 (1998
76. Brodde OE. Beta-Adrenoceptors in cardiac disease. Pharmacol. Ther. 60, 405-430 (1993
77. Koch WJ, Rockman HA, Samama P et al. Cardiac function in mice overexpressing the beta-Adrenergic receptor kinase or a beta ARK inhibitor. Science 268, 1350-1353 (1995
78. Koch WJ, Inglese J, Stone WC, Lefkowitz RJ. The binding site for the beta gamma subunits of heterotrimeric G proteins on the beta-Adrenergic receptor kinase. J. Biol. Chem. 268, 8256-8260 (1993
79. Akhter SA, Skaer CA, Kypson AP et al. Restoration of beta-Adrenergic signaling in failing cardiac ventricular myocytes via adenoviral-mediated gene transfer. Proc. Natl Acad. Sci. USA 94, 12100-12105 (1997
80. Williams ML, Hata JA, Schroder J et al. Targeted beta-Adrenergic receptor kinase (betaARK1) inhibition by gene transfer in failing human hearts. Circulation 109, 1590-1593 (2004
81. White DC, Hata JA, Shah AS, Glower DD, Lefkowitz RJ, Koch WJ. Preservation of myocardial beta-Adrenergic receptor signaling delays the development of heart failure after myocardial infarction. Proc. Natl Acad. Sci. USA 97, 5428-5433 (2000
82. Shah AS, White DC, Emani S et al. In vivo ventricular gene delivery of a beta-Adrenergic receptor kinase inhibitor to the failing heart reverses cardiac dysfunction. Circulation 103, 1311-1316 (2001
83. Rockman HA, Chien KR, Choi DJ et al. Expression of a beta-Adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice. Proc. Natl Acad. Sci. USA 95, 7000-7005 (1998
84. Harding VB, Jones LR, Lefkowitz RJ, Koch WJ, Rockman HA. Cardiac beta ARK1 inhibition prolongs survival and augments beta blocker therapy in a mouse model of severe heart failure. Proc. Natl Acad. Sci. USA 98, 5809-5814 (2001
85. Freeman K, Lerman I, Kranias EG et al. Alterations in cardiac adrenergic signaling and calcium cycling differentially affect the progression of cardiomyopathy. J. Clin. Invest. 107, 967-974 (2001
86. Raake PW, Vinge LE, Gao E et al. G protein-coupled receptor kinase 2 ablation in cardiac myocytes before or after myocardial infarction prevents heart failure. Circ. Res. 103, 413-422 (2008
87. Brinks H, Boucher M, Gao E et al. Level of G protein-coupled receptor kinase-2 determines myocardial ischemia/reperfusion injury via pro- And anti-Apoptotic mechanisms. Circ. Res. 107, 1140-1149 (2010
88. Chen M. Pro-death signaling of GRK2 in cardiac myocytes after ischemic stress occurs via ERK-dependent, Hsp90-mediated mitochondrial targeting. Circ. Res. 112, 300754 (2013
89. Rengo G, Lymperopoulos A, Zincarelli C et al. Myocardial adeno-Associated virus serotype 6-betaARKct gene therapy improves cardiac function and normalizes the neurohormonal axis in chronic heart failure. Circulation 119, 89-98 (2009
90. Raake PW, Schlegel P, Ksienzyk J et al. AAV6.?ARKct cardiac gene therapy ameliorates cardiac function and normalizes the catecholaminergic axis in a clinically relevant large animal heart failure model. Eur. Heart J. 34(19), 1437-1447 (2012
91. Engelhardt S, Grimmer Y, Fan GH, Lohse MJ. Constitutive activity of the human beta(1)-Adrenergic receptor in beta(1)- receptor transgenic mice. Mol. Pharmacol. 60, 712-717 (2001
92. Bisognano JD, Weinberger HD, Bohlmeyer TJ et al. Myocardial-directed overexpression of the human beta(1)-Adrenergic receptor in transgenic mice. J. Mol. Cell. Cardiol. 32, 817-830 (2000
93. Milano CA, Allen LF, Rockman HA et al. Enhanced myocardial function in transgenic mice overexpressing the beta 2-Adrenergic receptor. Science 264, 582-586 (1994
94. Maurice JP, Hata JA, Shah AS et al. Enhancement of cardiac function after adenoviral-mediated in vivo intracoronary beta2-Adrenergic receptor gene delivery. J. Clin. Invest. 104, 21-29 (1999
95. Jones JM, Petrofski JA, Wilson KH, Steenbergen C, Koch WJ, Milano CA. Beta2 adrenoceptor gene therapy ameliorates left ventricular dysfunction following cardiac surgery. Eur. J. Cardiothorac. Surg. 26, 1161-1168 (2004
96. Liggett SB, Tepe NM, Lorenz JN et al. Early and delayed consequences of beta(2)-Adrenergic receptor overexpression in mouse hearts: Critical role for expression level. Circulation 101, 1707-1714 (2000
97. Steinberg SF. The molecular basis for distinct beta-Adrenergic receptor subtype actions in cardiomyocytes. Circ. Res. 85, 1101-1111 (1999
98. Lai NC, Roth DM, Gao MH et al. Intracoronary delivery of adenovirus encoding adenylyl cyclase VI increases left ventricular function and cAMP-generating capacity. Circulation 102, 2396-2401 (2000
99. Lai NC, Roth DM, Gao MH et al. Intracoronary adenovirus encoding adenylyl cyclase VI increases left ventricular function in heart failure. Circulation 110, 330-336 (2004
100. Greener I, Donahue JK. Gene therapy strategies for cardiac electrical dysfunction. J. Mol. Cell. Cardiol. 50, 759-765 (2011
101. Sasano T, McDonald AD, Kikuchi K, Donahue JK. Molecular ablation of ventricular tachycardia after myocardial infarction. Nat. Med. 12, 1256-1258 (2006
102. Bikou O, Thomas D, Trappe K et al. Connexin 43 gene therapy prevents persistent atrial fibrillation in a porcine model. Cardiovasc. Res. 92, 218-225 (2011
103. Amit G, Kikuchi K, Greener ID, Yang L, Novack V, Donahue JK. Selective molecular potassium channel blockade prevents atrial fibrillation. Circulation 121, 2263-2270 (2010
104. Greener ID, Sasano T, Wan X et al. Connexin43 gene transfer reduces ventricular tachycardia susceptibility after myocardial infarction. J. Am. Coll. Cardiol. 60, 1103-1110 (2012
105. Lyon AR, Bannister ML, Collins T et al. SERCA2a gene transfer decreases sarcoplasmic reticulum calcium leak and reduces ventricular arrhythmias in a model of chronic heart failure. Circ. Arrhythm. Electrophysiol. 4, 362-372 (2011
106. Cutler MJ, Wan X, Plummer BN et al. Targeted sarcoplasmic reticulum Ca2+ ATPase 2a gene delivery to restore electrical stability in the failing heart. Circulation 126, 2095-2104 (2012
107. Qian L, Huang Y, Spencer CI et al. In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature 485, 593-598 (2012
108. Song K, Nam YJ, Luo X et al. Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature 485, 599-604 (2012
109. Jayawardena TM, Egemnazarov B, Finch EA et al. MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes. Circ. Res. 110, 1465-1473 (2012
110. Beeri R, Guerrero JL, Supple G, Sullivan S, Levine RA, Hajjar RJ. New efficient catheter-based system for myocardial gene delivery. Circulation 106, 1756-1759 (2002
111. French BA, Mazur W, Geske RS, Bolli R. Direct in vivo gene transfer into porcine myocardium using replication-deficient adenoviral vectors. Circulation 90, 2414-2424 (1994
112. Sasano T, Kikuchi K, McDonald AD, Lai S, Donahue JK. Targeted high-efficiency, homogeneous myocardial gene transfer. J. Mol. Cell. Cardiol. 42, 954-961 (2007
113. Hayase M, Del Monte F, Kawase Y et al. Catheter-based antegrade intracoronary viral gene delivery with coronary venous blockade. Am. J. Physiol. Heart Circ. Physiol. 288, H2995-H3000 (2005
114. White DC, Koch WJ. Myocardial gene transfer. Curr. Cardiol. Rep. 3, 37-42 (2001
115. Swain JD, Fargnoli AS, Katz MG et al. MCARD-mediated gene transfer of GRK2 inhibitor in ovine model of acute myocardial infarction. J. Cardiovasc. Transl. Res. 6, 253-262 (2013
116. Boekstegers P, von Degenfeld G, Giehrl W et al. Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins. Gene. Ther. 7, 232-240 (2000
117. Raake P, von Degenfeld G, Hinkel R et al. Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins: Comparison with surgical and percutaneous intramyocardial gene delivery. J. Am. Coll. Cardiol. 44, 1124-1129 (2004
118. Vassalli G, Büeler H, Dudler J, von Segesser LK, Kappenberger L. Adeno-Associated virus (AAV) vectors achieve prolonged transgene expression in mouse myocardium and arteries in vivo: A comparative study with adenovirus vectors. Int. J. Cardiol. 90, 229-238 (2003
119. Wan S, George SJ, Nicklin SA, Yim AP, Baker AH. Overexpression of p53 increases lumen size and blocks neointima formation in porcine interposition vein grafts. Mol. Ther. 9, 689-698 (2004
120. Ninomiya M, Koyama H, Miyata T et al. Ex vivo gene transfer of basic fibroblast growth factor improves cardiac function and blood flow in a swine chronic myocardial ischemia model. Gene. Ther. 10, 1152-1160 (2003
121. Kim C, Wong J, Wen J et al. Studying arrhythmogenic right ventricular dysplasia with patient-specific iPSCs. Nature 494, 105-110 (2013
122. McTiernan CF, Mathier MA, Zhu X et al. Myocarditis following adeno-Associated viral gene expression of human soluble TNF receptor (TNFRII-Fc) in baboon hearts. Gene. Ther. 14, 1613-1622 (2007
123. Shah PB, Losordo DW. Non-viral vectors for gene therapy: Clinical trials in cardiovascular disease. Adv. Genet. 54, 339-361 (2005
124. Nishi T, Yoshizato K, Yamashiro S et al. High-efficiency in vivo gene transfer using intraarterial plasmid DNA injection following in vivo electroporation. Cancer Res. 56, 1050-1055 (1996
125. Amabile PG, Waugh JM, Lewis TN, Elkins CJ, Janas W, Dake MD. Highefficiency endovascular gene delivery via therapeutic ultrasound. J. Am. Coll. Cardiol. 37, 1975-1980 (2001
126. Condon C, Watkins SC, Celluzzi CM, Thompson K, Falo LD. DNA-based immunization by in vivo transfection of dendritic cells. Nat. Med. 2, 1122-1128 (1996
127. Park JW, Kirpotin DB, Hong K et al. Tumor targeting using anti-her2 immunoliposomes. J. Control Release 74, 95-113 (2001
128. Park JW, Hong K, Carter P et al. Development of anti-p185HER2 immunoliposomes for cancer therapy. Proc. Natl Acad. Sci. USA 92, 1327-1331 (1995
129. Xu L, Anchordoquy T. Drug delivery trends in clinical trials and translational medicine: Challenges and opportunities in the delivery of nucleic acid-based therapeutics. J. Pharm. Sci. 100, 38-52 (2011
130. Malam Y, Lim EJ, Seifalian AM. Current trends in the application of nanoparticles in drug delivery. Curr. Med. Chem. 18, 1067-1078 (2011
131. Sofou S, Sgouros G. Antibody-targeted liposomes in cancer therapy and imaging. Expert Opin. Drug Deliv. 5, 189-204 (2008
132. Li S, Rizzo MA, Bhattacharya S, Huang L. Characterization of cationic lipid-protamine- DNA (LPD) complexes for intravenous gene delivery. Gene. Ther. 5, 930-937 (1998
133. Friend DS, Papahadjopoulos D, Debs RJ. Endocytosis and intracellular processing accompanying transfection mediated by cationic liposomes. Biochim. Biophys. Acta 1278, 41-50 (1996
134. Lutz J, Augustin AJ, Jäger LJ, Bachmann D, Brandl M. Acute toxicity and depression of phagocytosis in vivo by liposomes: Influence of lysophosphatidylcholine. Life Sci. 56, 99-106 (1995
135. Müller OJ, Katus HA, Bekeredjian R. Targeting the heart with gene therapyoptimized gene delivery methods. Cardiovasc. Res. 73, 453-462 (2007
136. Stankovics J, Crane AM, Andrews E, Wu CH, Wu GY, Ledley FD. Overexpression of human methylmalonyl CoA mutase in mice after in vivo gene transfer with asialoglycoprotein/polylysine/DNA complexes. Hum. Gene Ther. 5, 1095-1104 (1994
137. Xu B, Wiehle S, Roth JA, Cristiano RJ. The contribution of poly-L-lysine, epidermal growth factor and streptavidin to EGF/PLL/DNA polyplex formation. Gene. Ther. 5, 1235-1243 (1998
138. Klages N, Zufferey R, Trono D. A stable system for the high-titer production of multiply attenuated lentiviral vectors. Mol. Ther. 2, 170-176 (2000
139. Le Doux JM, Davis HE, Morgan JR, Yarmush ML. Kinetics of retrovirus production and decay. Biotechnol. Bioeng. 63, 654-662 (1999
140. Nabel EG. Gene therapy for cardiovascular disease. Circulation 91, 541-548 (1995
141. Matyas L, Schulte KL, Dormandy JA et al. Arteriogenic gene therapy in patients with unreconstructable critical limb ischemia: A randomized, placebo-controlled clinical trial of adenovirus 5-delivered fibroblast growth factor-4. Hum. Gene. Ther. 16, 1202-1211 (2005
142. Tongers J, Roncalli JG, Losordo DW. Therapeutic angiogenesis for critical limb ischemia: Microvascular therapies coming of age. Circulation 118, 9-16 (2008
143. Raper SE, Chirmule N, Lee FS et al. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol. Genet. Metab. 80, 148-158 (2003
144. Gonçalves MA. Adeno-Associated virus: From defective virus to effective vector. Virol. J. 2, 43 (2005
145. Bantel-Schaal U, zur Hausen H. Characterization of the DNA of a defective human parvovirus isolated from a genital site. Virology 134, 52-63 (1984
146. Grimm D, Kay MA. From virus evolution to vector revolution: Use of naturally occurring serotypes of adeno-Associated virus (AAV) as novel vectors for human gene therapy. Curr. Gene. Ther. 3, 281-304 (2003
147. Pacak CA, Mah CS, Thattaliyath BD et al. Recombinant adeno-Associated virus serotype 9 leads to preferential cardiac transduction in vivo. Circ. Res. 99, e3-e9 (2006
148. Zincarelli C, Soltys S, Rengo G, Rabinowitz JE. Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection. Mol. Ther. 16, 1073-1080 (2008
149. Inagaki K, Fuess S, Storm TA et al. Robust systemic transduction with AAV9 vectors in mice: Efficient global cardiac gene transfer superior to that of AAV8. Mol. Ther. 14, 45-53 (2006
150. Wang Z, Zhu T, Qiao C et al. Adenoassociated virus serotype 8 efficiently delivers genes to muscle and heart. Nat. Biotechnol. 23, 321-328 (2005
151. Zhu T, Zhou L, Mori S et al. Sustained whole-body functional rescue in congestive heart failure and muscular dystrophy hamsters by systemic gene transfer. Circulation 112, 2650-2659 (2005
152. Snyder RO, Miao C, Meuse L et al. Correction of hemophilia B in canine and murine models using recombinant adeno-Associated viral vectors. Nat. Med. 5, 64-70 (1999
153. Kessler PD, Podsakoff GM, Chen X et al. Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein. Proc. Natl Acad. Sci. USA 93, 14082-14087 (1996
154. Malik AK, Monahan PE, Allen DL, Chen BG, Samulski RJ, Kurachi K. Kinetics of recombinant adeno-Associated virus-mediated gene transfer. J. Virol. 74, 3555-3565 (2000
155. Nakai H, Storm TA, Kay MA. Recruitment of single-stranded recombinant adenoassociated virus vector genomes and intermolecular recombination are responsible for stable transduction of liver in vivo. J. Virol. 74, 9451-9463 (2000