Abstract
Heart diseases are a major cause of morbidity and mortality in contemporary society. Advances in the understanding of the molecular basis of myocardial dysfunction have placed many acquired and congenital cardiovascular diseases within the reach of gene-based therapy. Four prerequisites are required for a successful clinical application of gene therapy: (1) an effective strategy for genetic manipulation, (2) availability of vectors with enhanced myocardial tropism, (3) a clinically translatable delivery technique that will result in global or regional expression, and (4) creation of therapeutic transgenes for selected molecular targets depending on the underlying pathological state of the heart. Despite significant promise, however, several obstacles exist with gene-based therapies. These obstacles are described in detail in this chapter, along with proposed solutions. We anticipate that advances in the field will improve cardiac gene therapy in future clinical approaches.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Melo LG, Pachori AS, Gnecchi M, Dzau VJ (2005) Genetic therapies for cardiovascular diseases. Trends Mol Med 11:240–250
Quarck R, Holvoet P (2004) Gene therapy approaches for cardiovascular diseases. Curr Gene Ther 4:207–223
Morishita R (2004) Perspective in progress of cardiovascular gene therapy. J Pharmacol Sci 95:1–8
Quarck R, De Geest B, Stengel D, Mertens A, Lox M, Theilmeier G et al (2001) Adenovirus-mediated gene transfer of human platelet-activating factor-acetylhydrolase prevents injury-induced neointima formation and reduces spontaneous atherosclerosis in apolipoprotein E-deficient mice. Circulation 103:2495–2500
Marchand GS, Noiseux N, Tanguay J-F, Sirois MG (2002) Blockade of in vivo VEGF-mediated angiogenesis by antisense gene therapy: role of Flk-1 and Flt-1 receptors. Am J Physiol Heart Circ Physiol 282:H194–H204
Montgomery RL, Hullinger TG, Semus HM, Dickinson BA, Seto AG, Lynch JM et al (2011) Therapeutic inhibition of miR-208a improves cardiac function and survival during heart Âfailure. Circulation 124:1537–1547
Kawauchi M, Suzuki J, Morishita R, Wada Y, Izawa A, Tomita N et al (2000) Gene therapy for attenuating cardiac allograft arteriopathy using ex vivo E2F decoy transfection by HVJ-ÂAVE-liposome method in mice and nonhuman primates. Circ Res 87:1063–1068
Yamasaki K, Asai T, Shimizu M, Aoki M, Hashiya N, Sakonjo H et al (2003) Inhibition of NFkappaB activation using cis-element ‘decoy’ of NFkappaB binding site reduces neointimal formation in porcine balloon-injured coronary artery model. Gene Ther 10:356–364
Suckau L, Fechner H, Chemaly E, Krohn S, Hadri L, Kockskämper J et al (2009) Long-term cardiac-targeted RNA interference for the treatment of heart failure restores cardiac function and reduces pathological hypertrophy. Circulation 119:1241–1252
Tsunoda S, Mazda O, Oda Y, Iida Y, Akabame S, Kishida T et al (2005) Sonoporation using microbubble BR14 promotes pDNA/siRNA transduction to murine heart. Biochem Biophys Res Commun 336:118–127
Rinne A, Littwitz C, Kienitz M-C, Gmerek A, Bösche LI, Pott L et al (2006) Gene silencing in adult rat cardiac myocytes in vitro by adenovirus-mediated RNA interference. J Muscle Res Cell Motil 27:413–421
Macejak DG, Lin H, Webb S, Chase J, Jensen K, Jarvis TC et al (1999) Adenovirus-mediated expression of a ribozyme to c-mybmRNA inhibits smooth muscle cell proliferation and neointima formation in vivo. J Virol 73:7745–7751
Yamamoto K, Morishita R, Tomita N, Shimozato T, Nakagami H, Kikuchi A et al (2000) Ribozyme oligonucleotides against TGF-b inhibited neointimal formation after vascular injury in rat model: potential application of ribozyme strategy to treat cardiovascular disease. Circulation 102:1308–1314
Gaffney MM, Hynes SO, Barry F, O’Brien T (2007) Cardiovascular gene therapy: current status and therapeutic potential. Br J Pharmacol 152:175–188
Müller OJ, Ksienzyk J, Katus HA (2008) Gene-therapy delivery strategies in cardiology. Future Cardiol 4:135–150
Felgner PL, Barenholz Y, Behr JP, Cheng SH, Cullis P, Huang L et al (1997) Nomenclature for synthetic gene delivery systems. Hum Gene Ther 8:511–512
Lin H, Parmacek MS, Morle G, Bolling S, Leiden JM (1990) Expression of recombinant genes in myocardium in vivo after direct injection of DNA. Circulation 82:2217–2221
Acsadi G, Jiao SS, Jani A, Duke D, Williams P, Chong W et al (1991) Direct gene transfer and expression into rat heart in vivo. New Biol 3:71–81
Nabel EG (1995) Gene therapy for cardiovascular disease. Circulation 91:541–548
Isner JM (2002) Myocardial gene therapy. Nature 415:234–239
Losordo DW, Vale PR, Symes JF, Dunnington CH, Esakof DD, Maysky M et al (1998) Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF 165 as sole therapy for myocardial ischemia. Circulation 98:2800–2804
Vale PR, Losordo DW, Milliken CE, McDonald MC, Gravelin LM, Curry CM et al (2001) 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
Kastrup J, Jørgensen E, Rück A, Tägil K, Glogar D, Rusyllo W et al (2005) Direct intramyocardial plasmid VEGF-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
Qin L, Pahud DR, Ding Y, Bielinska AU, Kukowska-Latallo JF, Baker JR et al (1998) Efficient transfer of genes into murine cardiac grafts by Starburst polyamidoamine dendrimers. Hum Gene Ther 9:553–560
Kizana E, Alexander IE (2003) Cardiac gene therapy: therapeutic potential and current Âprogress. Curr Gene Ther 3:418–451
Wasala NB, Shin J-H, Duan D (2011) The evolution of heart gene delivery vectors. J Gene Med 13:557–565
Vinge LE, Raake PW, Koch WJ (2008) Gene therapy in heart failure. Circ Res 102:1458–1470
Hinkel R, Trenkwalder T, Kupatt C (2011) Gene therapy for ischemic heart disease. Expert Opin Biol Ther 11:723–737
Rapti K, Chaanine AH, Hajjar RJ (2011) Targeted gene therapy for the treatment of heart failure. Can J Cardiol 27:265–283
Ding W, Zhang L, Yan Z, Engelhardt JF (2005) Intracellular trafficking of adeno-associated viral vectors. Gene Ther 12:873–880
Zhao J, Pettigrew GJ, Thomas J, Vandenberg JI, Delriviere L, Bolton EM et al (2002) Lentiviral vectors for delivery of genes into neonatal and adult ventricular cardiac myocytes in vitro and in vivo. Basic Res Cardiol 97:348–358
Bonci D, Cittadini A, Latronico MV, Borello U, Aycock JK, Drusco A et al (2003) ‘Advanced’ generation lentiviruses as efficient vectors for cardiomyocyte gene transduction in vitro and in vivo. Gene Ther 10:630–636
Fleury S, Simeoni E, Zuppinger C, Deglon N, von Segesser LK, Kappenberger L, Vassalli G (2003) Multiply attenuated, self-inactivating lentiviral vectors efficiency deliver and express genes for extended periods of time in adult rat cardiomyocytes in vivo. Circulation 197:2375–2382
Niwano K, Arai M, Koitabashi N, Watanabe A, Ikeda Y, Miyoshi H et al (2008) Lentiviral vector-mediated SERCA2 gene transfer protects against heart failure and left ventricular remodeling after myocardial infarction in rats. Mol Ther 16:1002–1004
Guzman RJ, Lemarchand P, Crystal RG, Epstein SE, Finkel T (1993) Efficient gene transfer into myocardium by direct injection of adenovirus vectors. Circ Res 73:1202–1207
Kass-Eisler A, Falck-Pedersen E, Alvira M, Rivera J, Buttrick PM, Wittenberg BA et al (1993) Quantitative determination of adenovirus-mediated gene delivery to rat cardiac myocytes in vitro and in vivo. Proc Natl Acad Sci USA 90:11498–11502
French BA, Mazur W, Geske RS, Bolli R (1994) Direct in vivo gene transfer into porcine myocardium using replication-deficient adenoviral vectors. Circulation 90:2414–2424
Hajjar RJ, Schmidt U, Matsui T, Guerrero JL, Lee KH, Gwathmey JK et al (1998) Modulation of ventricular function through gene transfer in vivo. Proc Natl Acad Sci USA 95:5251–5256
Maurice JP, Hata JA, Shah AS, White DC, McDonald PH, Dolber PC et al (1999) Enhancement of cardiac function after adenoviral-mediated in vivo intracoronary β2-adrenergic receptor gene delivery. J Clin Invest 104:21–29
Berns KI, Giraud C (1996) Biology of adeno-associated virus. Curr Top Microbiol Immunol 218:1–23
Samulski RJ, Berns KI, Tan M, Muzyczka N (1982) Cloning of adeno-associated virus into pBR322: rescue of intact virus from the recombinant plasmid in human cells. Proc Natl Acad Sci USA 79:2077–2081
Laughlin CA, Tratschin JD, Coon H, Carter BJ (1983) Cloning of infectious adeno-associated virus genomes in bacterial plasmids. Gene 23:65–73
Rivera VM, Gao GP, Grant RL, Schnell MA, Zoltick PW, Rozamus LW et al (2005) Long-term pharmacologically regulated expression of erythropoietin in primates following AAV-mediated gene transfer. Blood 105:1424–1430
Coura Rdos S, Nardi NB (2007) The state of the art of adeno-associated virus-based vectors in gene therapy. Virol J 4:99
Ziello JE, Huang Y, Jovin IS (2010) Cellular endocytosis and gene delivery. Mol Med 16:222–229
Coura RS, Nardi NB (2008) A role for adeno-associated viral vectors in gene therapy. Gene Mol Biol 31:1–11
Di Pasquale G, Chiorini JA (2006) AAV transcytosis through barrier epithelia and Âendothelium. Mol Ther 13:506–516
Wang Z, Zhu T, Qiao C, Zhou L, Wang B, Zhang J et al (2005) Adeno-associated virus Âserotype 8 efficiently delivers genes to muscle and heart. Nat Biotechnol 23:321–328
Melo LG, Agraval R, Zhang L, Rezvani M, Mangi AA et al (2002) Gene therapy strategy for long-term myocardial protection using adeno-associated virus-mediated delivery of heme Âoxygenase gene. Circulation 105:602–607
Gregorovic P, Blankinship MJ, Allen JM, Crawford RW, Meuse L, Miller DG et al (2004) Systemic delivery of genes to striated muscles using adeno-associated viral vectors. Nat Med 10:828–834
Wang J, Faust SM, Rabinowitz JE (2011) The next step in gene delivery: molecular engineering of adeno-associated virus serotypes. J Mol Cell Cardiol 50:793–802
Müller OJ, Katus HA, Bekeredjian R (2007) Targeting the heart with gene therapy-optimized gene delivery methods. Cardiovasc Res 73:453–462
Katz MG, Swain JD, Tomasulo CE, Sumaroka M, Fargnoli A, Bridges CR (2011) Current strategies for myocardial gene delivery. J Mol Cell Cardiol 50:766–776
Katz MG, Fargnoli AS, Pritchette LA, Bridges CR (2012) Gene delivery technologies for cardiac applications. Gene Ther 19(6):659–669
Buttrick PM, Kass A, Kitsis RN, Kaplan ML, Leinwand LA (1992) Behavior of genes directly injected into the rat heart in vivo. Circ Res 70:193–198
Tomiyasu K, Oda Y, Nomura M, Satoh E, Fushiki S, Imanishi J et al (2000) Direct intracardiomuscular transfer of β2-adrenergic receptor gene augments cardiac output in cardiomyopathic hamsters. Gene Ther 7:2087–2093
Rengo G, Lymperopoulos A, Zincarelli C, Donniacuo M, Soltys S, Rabinowitz JE et al (2009) Myocardial adeno-associated virus serotype 6-bARKct gene therapy improves cardiac function and normalizes the neurohormonal axis in chronic heart failure. Circulation 119:89–98
Pätilä T, Ikonen T, Rutanen J, Ahonen A, Lommi J, Lappalainen K et al (2006) Vascular endothelial growth factor C-induced collateral formation in a model of myocardial ischemia. J Heart Lung Transplant 25:206–213
Schwarz ER, Speakman MT, Patterson M, Hale SS, Isner JM, Kedes LH et al (2000) Evaluation of the effects of intramyocardial injection of DNA expressing vascular endothelial growth Âfactor in a myocardial infarction model in the rat-angiogenesis and angioma formation. J Am Coll Cardiol 35:1323–1330
Vera Janavel GL, De Lorenzi A, Cortes C, Olea FD, Cabeza Meckert P, Bercovich A et al (2012) Effect of VEGF gene transfer on infarct size, left ventricular function and myocardial perfusion in sheep after two months of coronary artery occlusion. J Gene Med 14(4):279–287
Edelberg JM, Huang DT, Josephson ME, Rosenberg RD (2001) Molecular enhancement of porcine cardiac chronotropy. Heart 86:559–562
Grossman PM, Han Z, Palasis M, Barry JJ, Lederman RJ (2002) Incomplete retention after direct myocardial injection. Catheter Cardiovasc Interv 55:392–397
Bish LT, Sleeper MM, Braibard B, Cole S, Russell N, Withnall E et al (2000) Percutaneous transendocardial delivery of self-complementary AAV6 achieves global cardiac gene transfer in canines. Mol Ther 16:1953–1959
von Harsdorf R, Schott RJ, Shen YT, Vatner SF, Mahdavi V, Nadal-Ginard B (1993) Gene injection into canine myocardium as a useful model for studying gene expression in the heart of large mammals. Circ Res 72:688–695
Hedman M, Hartikainen J, Ylä-Herttuala S (2011) Progress and prospects: hurdles to cardiovascular gene therapy clinical trials. Gene Ther 18:743–749
Rosengart TK, Lee LY, Patel SR, Sanborn TA, Parikh M, Bergman GW et al (1999) Angiogenesis gene therapy: phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEFG 121 cDNA to individuals with clinically significant severe coronary artery disease. Circulation 100:468–474
Lamping KG, Rios CD, Chun JA, Ooboshi H, Davidson BL, Heistad DD (1997) Intrapericardial administration of adenovirus for gene transfer. Am J Physiol 272:H310–H317
March KL, Woody M, Mehdi K, Zipes DP, Brantly M, Trapnell BC (1999) Efficient in vivo Âcatheter-based pericardial gene transfer mediated by adenoviral vectors. Clin Cardiol 22:123–129
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 6:683–688
Lazarous DF, Shou M, Stiber JA, Hodge E, Thirumurti V, Goncalves L et al (1999) Adenoviral-mediated gene transfer induces sustained pericardial VEGF expression in dogs: effect on myocardial angiogenesis. Cardiovasc Res 44:294–302
Zhang JCL, Woo YJ, Chen JA, Swain JL, Sweeney HL (1999) Efficient transmural cardiac gene transfer by intrapericardial injection in neonatal mice. J Mol Cell Cardiol 31:721–732
Mühlhauser J, Jones M, Yamada I, Cirielli C, Lemarchand P, Gloe TR et al (1996) Safety and efficacy of in vivo gene transfer into the porcine heart with replication-deficient, recombinant adenovirus vectors. Gene Ther 3:145–153
Logeart D, Hatem SN, Heimburger M, Roux AL, Michel JB, Mercadier JJ (2001) How to optimize in vivo gene transfer to cardiac myocytes: mechanical or pharmacological procedures? Hum Gene Ther 12:1601–1610
Kaplitt MG, Xiao X, Samulski RJ, Li J, Ojamaa K, Klein IL et al (1996) Long-term gene transfer in porcine myocardium after coronary infusion of an adeno-associated virus vector. Ann Thorac Surg 62:1669–1676
Logeart D, Hatem SN, Rücker-Martin C, Chossat N, Nevo N, Haddada H et al (2000) Highly efficient adenovirus-mediated gene transfer to cardiac myocytes after single-pass coronary delivery. Hum Gene Ther 11:1015–1022
Hayase M, del Monte F, Kawase Y, MacNeill BD, McGregor J, Yoneyama R et al (2005) Catheter-based antegrade intracoronary viral gene delivery with coronary venous blockade. Am J Physiol Heart Circ Physiol 288:H2995–H3000
Ding Z, Fach C, Sasse A, Gődecke A, Schrader J (2004) A minimally invasive approach for efficient gene delivery to rodent hearts. Gene Ther 11:260–265
Wright MJ, Wightman LML, Latchman DS, Marber MS (2001) In vivo myocardial gene transfer: optimization and evaluation of intracoronary gene delivery in vivo. Gene Ther 8:1833–1839
Emani SM, Shah AS, Bowman MK, Emani S, Wilson K, Glower DD et al (2003) Catheter-based intracoronary myocardial adenoviral gene delivery: importance of intraluminal seal and infusion flow rate. Mol Ther 8:306–313
Donahue JK, Kikkawa K, Johns DC, Marban E, Lawrence JH (1997) Ultrarapid, highly efficient viral gene transfer to the heart. Proc Natl Acad Sci USA 94:4664–4668
Kaspar BK, Roth DM, Lai NC, Drumm JD, Erickson DA, McKirnan MD, Hammond HK (2005) Myocardial gene transfer and long-term expression following intracoronary delivery of adeno-associated virus. J Gene Med 7:316–324
Parsa CJ, Reed RC, Walton GB, Pascal LS, Thompsom RB, Petrofski JA et al (2005) Catheter-mediated subselective intracoronary gene delivery to the rabbit heart: introduction of a novel method. J Gene Med 7:595–603
Boekstegers P, Kupatt C (2004) Current concepts and applications of coronary venous retroinfusions. Basic Res Cardiol 99:373–381
Boekstegers P, von Degenfeld G, Giehrl W, Heinrich D, Hullin R, Kupatt C et al (2000) Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins. Gene Ther 7:232–240
von Degenfeld G, Raake P, Kupatt C, Lebherz C, Hinkel R, Gildehaus FJ et al (2003) Selective pressure-regulated retroinfusion of FGF-2 into the coronary vein enhances regional myocardial blood flow and function in pigs with chronic myocardial ischemia. J Am Coll Cardiol 42:1120–1128
Kuppat C, Hinkel R, Vachenauer R, Horstkotte J, Raake P, Sandner T et al (2003) VEGF 165 transfection decreases postischemic NF-kappa B-dependent myocardial reperfusion injury in vivo: role eNOS phosphorylation. FASEB J 17:705–707
Lassaletta AD, Chu LM, Sellke FW (2011) Therapeutic neovascularization for coronary disease: current state and future prospects. Basic Res Cardiol 106:897–909
Rome JJ, Shayani V, Newmark KD, Farrell S, Lee SW, Virmani R et al (1994) Adenoviral vector mediated gene transfer into sheep arteries using a double balloon catheter. Hum Gene Ther 5:1249–1258
Flugelman MY, Jaklitsch MT, Newman KD, Casscells W, Bratthauer GL, Dichek DA (1992) Low level in vivo gene transfer into the arterial wall through a perforated balloon catheter. Circulation 85:1110–1117
Tahlil O, Brami M, Feldman LJ, Branellec D, Steg PG (1997) The Dispatch catheter as a delivery tool for arterial tool for arterial gene transfer. Cardiovasc Res 33:181–187
Pavlides GS, Barath P, Maginas A, Vasilikos V, Cokkinos DV, O’Neill WW (1997) Intramural drug delivery by direct injection within arterial wall: first clinical experience with a novel intracoronary delivery-infiltrator system. Cathet Cardiovasc Diagn 41:287–292
Sharif F, Hynes SO, McMahon J, Cooney R, Conroy S, Dockery P et al (2006) Gene-eluting stents: comparison of adenoviral and adeno-associated viral gene delivery to the blood vessel wall in vivo. Hum Gene Ther 17:741–750
Fishbein I, Alferiev IS, Nyanguile O, Gaster R, Vohs JM, Wong GS et al (2006) Bisphosphonate-mediated gene vector delivery from the metal surfaces of stents. Proc Natl Acad Sci USA 103:159–164
Perstein I, Connolly JM, Cui X, Song C, Li Q, Jones PL et al (2003) DNA delivery from an intravascular stent with a denatured collagen-polylactic-polyglycolic acid-controlled release coating: mechanisms of enhanced transfection. Gene Ther 10:1420–1428
Lemos PA, Serruys PW, Sousa JE (2003) Drug-eluting stents: cost versus clinical benefit. Circulation 107:3003–3007
Lee J, Laks H, Drinkwater DC, Blitz A, Lam L, Shiraishi Y et al (1996) Cardiac gene transfer by intracoronary infusion of adenovirus vector-mediated reporter gene in the transplanted mouse heart. J Thorac Cardiovasc Surg 111:246–252
Kypson AP, Peppel K, Akhter SA, Lilly RE, Glower DD, Lefkowitz RJ et al (1998) Ex vivo adenovirus-mediated gene transfer to the adult rat heart. J Thorac Cardiovasc Surg 115:623–630
Griscelli F, Belli E, Opolon P, Musset K, Connault E, Perricaudet M et al (2003) Adenovirus-mediated gene transfer to the transplanted piglet heart after intracoronary injection. J Gene Med 5:109–119
Wang J, Ma Y, Knechtle SJ (1996) Adenovirus-mediated gene transfer into rat cardiac allografts: comparison of direct injection and perfusion. Transplantation 61:1726–1729
Shah AS, White DC, Tai O, Hata JA, Wilson KH, Pippen A et al (2000) Adenovirus-mediated genetic manipulation of the myocardial β-adrenergic signaling system in transplanted hearts. J Thorac Cardiovasc Surg 120:581–588
Bridges CR, Burkman JM, Malekan R, Konig SM, Chen H, Yarnall CB et al (2002) Global cardiac-specific transgene expression using cardiopulmonary bypass with cardiac isolation. Ann Thorac Surg 73:1939–1946
Davidson MJ, Jones JM, Emani SM, Wilson KH, Jaggers J, Koch WJ et al (2001) Cardiac gene delivery with cardiopulmonary bypass. Circulation 104:131–133
Jones JM, Wilson KH, Koch WJ, Milano CA (2002) Adenoviral gene transfer to the heart during cardiopulmonary bypass: effect of myocardial protection technique on transgene expression. Eur J Cardiothorac Surg 21:847–852
Ikeda Y, Gu Y, Iwanada Y, Hoshijima M, Oh SS, Giordano FJ et al (2002) Restoration of deficient membrane proteins in the cardiomyopathic hamster by in vivo cardiac gene transfer. Circulation 105:502–508
White JD, Thesier DM, Swain JD, Katz MG, Tomasulo CE, Henderson A et al (2011) Myocardial gene delivery using molecular cardiac surgery with recombinant adeno-associated virus vectors in vivo. Gene Ther 18:546–552
Fargnoli AS, Katz MG, Yarnall C, Sumaroka MV, Stedman H, Rabinowitz JE et al (2011) A Pharmacokinetic analysis of molecular cardiac surgery with recirculation mediated delivery of BARKct gene therapy: developing a quantitative definition of the therapeutic window. J Card Fail 17:691–699
Kaye DM, Preovolos A, Marshall BS, Byrne M, Hoshijima M, Hajjar RJ et al (2007) 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
Bridges CR (2009) Recirculating method of cardiac gene delivery should be called ‘non-recirculating’ method. Gene Ther 16:939–940
Shohet RV, Chen S, Zhou Y-T, Wang Z, Meidell RS, Unger RH, Grayburn PA (2000) Echocardiographic destruction of albumin microbubbles directs gene delivery to the myocardium. Circulation 101:2554–2556
Bekeredjian R, Chen S, Frenkel PA, Grayburn PA, Shohet RV (2003) Ultrasound-targeted microbubbles destruction can repeatedly direct highly specific plasmid expression to the heart. Circulation 108:1022–1026
Beeri R, Guerrero JL, Supple G, Sullivan S, Levine RA, Hajjar RJ (2002) New efficient catheter-based system for myocardial gene delivery. Circulation 106:1756–1759
Marshall WG, Boone BA, Burgos JD, Gografe SI, Baldwin MK, Danielson ML et al (2010) Electroporation-mediated delivery of a naked DNA plasmid expressing VEGF to the porcine heart enhances protein expression. Gene Ther 17:419–423
Ayuni EL, Gazdhar A, Giraud MN, Kadner A, Gugger M, Cecchini M et al (2010) In vivo electroporation mediated gene delivery to the beating heart. PLoS One 5:e14467
Kumar A, Jena PK, Bahera S, Lockey RF, Mohapatra S, Mohapatra S (2010) Multifunctional magnetic nanoparticles for targeted delivery. Nanomedicine 6:64–69
Polyak B, Fishbein I, Chorny M, Alferiev I, Williams D, Yellen B et al (2008) High field gradient targeting of magnetic nanoparticle-loaded endothelial cells to the surfaces of steel stents. Proc Natl Acad Sci USA 15:698–703
Sanborn TA, Hackett NR, Lee LY, El-Sawy T, Blanko I, Tarazona N et al (2001) Percutaneous endocardial transfer and expression of genes to the myocardium utilizing fluoroscopic guidance. Catheter Cardiovasc Interv 52:260–266
Gwon HC, Jeong JO, Kim HJ, Park SW, Lee SH, Park SJ et al (2001) The feasibility and safety of fluoroscopy-guided percutaneous intramyocardial gene injection in porcine heart. Int J Cardiol 79:77–88
Lederman RJ, Guttman MA, Peters DC, Thompson RB, Sorger JM, Dick AJ et al (2002) Catheter-based endomyocardial injection with real-time magnetic resonance imaging. Circulation 105:1282–1284
Kornowski R, Leon MB, Fuchs S, Vodovotz Y, Flynn MA, Gordon DA et al (2000) Electromagnetic guidance for catheter-based transendocardial injection: a platform for intramyocardial angiogenesis therapy. Results in normal and ischemic porcine models. J Am Coll Cardiol 35:1031–1039
Baklanov DV, de Muinck ED, Simons M, Moodie KL, Arbuckle BE, Thompson CA et al (2005) Live 3D echo guidance of catheter-based endomyocardial injection. Catheter Cardiovasc Interv 65:340–345
Davia K, Bernovich E, Ranu HK, del Monte F, Terracciano CM, MacLeod KT et al (2001) SERCA2a overexpression decreases the incidence of aftercontractions in adult rabbit ventricular myocytes. J Mol Cell Cardiol 33:1005–1015
del Monte F, Lebeche D, Guerrero JL, Tsuji T, Doye AA, Gwathmey JK et al (2004) Abrogation of ventricular arrhythmias in a model of ischemia and reperfusion by targeting myocardial calcium cycling. Proc Natl Acad Sci USA 101:5622–5627
Byrne MJ, Power JM, Preovolos A, Mariani JA, Hajjar RJ, Kaye DM (2008) Recirculating cardiac delivery of AAV2/1SERCA2a improves myocardial function in an experimental model of heart failure in large animals. Gene Ther 15:1550–1557
Jessup M, Greenberg B, Mancini D, Cappola T, Pauly DF, Jaski B et al (2011) Calcium upregulation by percutaneous administration of gene therapy in cardiac disease (CUPID). Circulation 124:304–313
Most P, Remppis A, Pleger ST, Katus HA, Koch WJ (2007) 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
Pleger ST, Most P, Boucher M, Soltys S, Chuprun JK, Pleger W et al (2007) Stable myocardial-specific AAV-S100A1 gene therapy results in chronic functional heart failure rescue. Circulation 115:2506–2515
Pleger ST, Shan C, Klienzyk J, Bekeredjian R, Boekstegers P, Hinkel R et al (2011) Cardiac AAV9-S100A1 Gene therapy rescues post-ischemic heart failure in a preclinical large animal model. Sci Transl Med 3:92ra64
Iwanaga Y, Hoshijima M, Gu Y, Iwatate M, Dieterle T, Ikeda Y et al (2004) Chronic phospholamban inhibition prevents progressive cardiac dysfunction and pathological remodeling after infarction in rats. J Clin Invest 113:727–736
Tsuji T, del Monte F, Yoshikawa Y, Abe T, Shimizu J, Nakajima-Takenaka C et al (2009) Rescue of Ca2+ overload-induced left ventricular dysfunction by targeted ablation of phospholamban. Am J Physiol Heart Circ Physiol 296:H310–H317
Rockman HA, Koch WJ, Lefkowitz RJ (2002) Seven-transmembrane-spanning receptors and heart function. Nature 415:206–212
Brodde OE (1993) Beta-adrenoreceptors in cardiac disease. Pharmacol Ther 60:405–430
Koch WJ, Rockman HA, Samama P, Hamilton RA, Bond RA, Milano CA et al (1995) Cardiac function in mice overexpressing the β-adrenergic receptor kinase or a βARK inhibitor. Science 268:1350–1353
Brinks H, Koch WJ (2010) βARKct: a therapeutic approach for improved adrenergic signaling and function in heart disease. J Cardiovasc Transl Res 3:499–506
White DC, Hata JA, Shah AS, Glower DD, Lefkowitz R, Koch WJ (2000) Preservation of myocardial b-adrenergic receptor signaling delays the development of heart failure after myocardial infarction. Proc Natl Acad Sci USA 97:5428–5433
Tevaearai HT, Walton GB, Keys JR, Koch WJ, Eckhart AD et al (2005) Acute ischemic cardiac dysfunction is attenuated via gene transfer of a peptide inhibitor of the b-adrenergic receptor kinase (βARK1). J Gene Med 7:1172–1177
Tachibana H, Naga Prasad SV, Lefkowitz RJ, Koch WJ, Rockman HA (2005) Level of b-adrenergic receptor kinase 1 inhibition determines degree of cardiac dysfunction after chronic pressure-overload-induced heart failure. Circulation 111:591–597
Lavu M, Gundewar S, Lefer DJ (2011) Gene therapy for ischemic heart disease. J Mol Cell Cardiol 50:742–750
Josko J, Gwozdz B, Jedrzejowska-Szypulka H, Hendryk S (2000) Vascular endothelial growth factor (VEGF) and its effect on angiogenesis. Med Sci Monit 6:1047–1052
Bull DA, Bailey SH, Rentz JJ, Zebrack JS, Lee M, Litwin SE et al (2003) Effect of Terplex/VEGF-165 gene therapy on left ventricular function and structure following myocardial infarction. VEGF gene therapy for myocardial infarction. J Control Release 93:175–181
Vera Javanel GL, Crottogini A, Cabeza Meckert P, Cuniberti L, Mele A, Papouchado M et al (2006) Plasmid-mediated VEGF gene transfer induces cardiomyogenesis and reduces myocardial infarct size in sheep. Gene Ther 13:1133–1142
Lähteenvuo JE, Lähteenvuo MT, Kivelä A, Rosenlew C, Falkevall A, Klar J et al (2009) Vascular endothelial growth factor-B induces myocardium-specific angiogenesis and arteriogenesis via vascular endothelial growth factor receptor-1- and neuropilin receptor-1- dependent mechanisms. Circulation 119:845–856
Ferrarini M, Arsic N, Recchia FA, Zentilin L, Zacchigna S, Xu X et al (2006) Adeno-associated virus-mediated transduction of VEGF 165 improves cardiac tissue viability and functional recovery after permanent coronary occlusion in conscious dogs. Circ Res 98:954–961
Rissanen TT, Ylä-Herttuala S (2007) Current status of cardiovascular gene therapy. Mol Ther 15:1233–1247
Lazarous DF, Scheinowitz M, Shou M, Hodge E, Rajanayagam S, Hunsberger S et al (1995) Effects of chronic systemic administration of basic fibroblast growth factor on collateral development in the canine heart. Circulation 91:145–153
Gao MH, Lai NC, McKirnan MD, Roth DA, Rubanyi GM, Roth DM, Hammond HK (2004) Increased regional function and perfusion after intracoronary delivery of adenovirus encoding FGF4: report of preclinical data. Hum Gene Ther 15:574–587
Suzuki G, Lee TC, Fallavollita JA, Canty JM (2005) 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
Henry TD, Grines CL, Watkins MW, Barbeau G, Moreadith R, Andrasfay T, Engler RL (2007) Effects of Ad5FGF-4 in patients with angina: an analysis of pooled data from the AGENT-3 and AGENT-4 trials. J Am Coll Cardiol 50:1038–1046
Donahue JK (2004) Gene therapy for cardiac arrhythmias. Ann N Y Acad Sci 1015:332–337
Donahue JK, Heldman AW, Fraser H, McDonald AD, Miller JM, Rade JJ et al (2000) Focal modification of electrical conduction in the heart by viral gene transfer. Nat Med 6:1395–1398
Bunch TJ, Mahapatra S, Bruce GK, Johnson SB, Miller DV, Horne BD et al (2006) Impact of transforming growth factor-beta1 on atrioventricular node conduction modification by injected autologous fibroblasts in the canine heart. Circulation 113:2485–2494
Edelberg JM, Aird WC, Rosenberg RD (1998) Enhancement of murine cardiac chronotropy by the molecular transfer of the human beta2 adrenergic receptor cDNA. J Clin Invest 101:337–343
Plotnikov AN, Sosunov EA, Qu J, Shlapakova IN, Anyukhovsky EP, Liu L et al (2004) Biological pacemaker implanted in canine left bundle branch provides ventricular escape rhythms that have physiologically acceptable rates. Circulation 109:506–512
Brunner M, Kodirov SA, Mitchell GF, Buckett PD, Shibata K, Folco EJ et al (2003) In vivo gene transfer of Kv1.5 normalized action potential duration and shortens QT interval in mice with long QT phenotype. Am J Physiol Heart Circ Physiol 285:H194–H203
Sasano T, McDonald AD, Kikuchi K, Donahue JK (2006) Molecular ablation of ventricular tachycardia after myocardial infarction. Nat Med 12:1256–1258
Kawada T, Nakazawa M, Nakauchi S, Yamazaki K, Shimamoto R, Urabe M (2002) Rescue of hereditary form of dilated cardiomyopathy by rAAV-mediated somatic gene therapy: amelioration of morphological findings, sarcolemmal permeability, cardiac performance and the prognosis of TO-2 hamsters. Proc Natl Acad Sci USA 99:901–906
Nuss HB, Marban E, Johns DC (1999) Overexpression of a human potassium channel suppresses cardiac hyperexcitability in rabbit ventricular myocytes. J Clin Invest 103:889–896
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media New York
About this chapter
Cite this chapter
Katz, M.G., Fargnoli, A.S., Pritchette, L.A., Bridges, C.R. (2013). Gene Transfer to the Heart: Emerging Strategies for the Selection of Vectors, Delivery Techniques, and Therapeutic Targets. In: Danquah, M., Mahato, R. (eds) Emerging Trends in Cell and Gene Therapy. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-417-3_8
Download citation
DOI: https://doi.org/10.1007/978-1-62703-417-3_8
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-62703-416-6
Online ISBN: 978-1-62703-417-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)