title: Targeted gene therapy for the treatment of heart failure.
abstract: Chronic heart failure is one of the leading causes of morbidity and mortality in Western countries and is a major financial burden to the health care system. Pharmacologic treatment and implanting devices are the predominant therapeutic approaches. They improve survival and have offered significant improvement in patient quality of life, but they fall short of producing an authentic remedy. Cardiac gene therapy, the introduction of genetic material to the heart, offers great promise in filling this void. In-depth knowledge of the underlying mechanisms of heart failure is, obviously, a prerequisite to achieve this aim. Extensive research in the past decades, supported by numerous methodological breakthroughs, such as transgenic animal model development, has led to a better understanding of the cardiovascular diseases and, inadvertently, to the identification of several candidate genes. Of the genes that can be targeted for gene transfer, calcium cycling proteins are prominent, as abnormalities in calcium handling are key determinants of heart failure. A major impediment, however, has been the development of a safe, yet efficient, delivery system. Nonviral vectors have been used extensively in clinical trials, but they fail to produce significant gene expression. Viral vectors, especially adenoviral, on the other hand, can produce high levels of expression, at the expense of safety. Adeno-associated viral vectors have emerged in recent years as promising myocardial gene delivery vehicles. They can sustain gene expression at a therapeutic level and maintain it over extended periods of time, even for years, and, most important, without a safety risk.
authors: Cardiovascular Research Center, Mount Sinai School of Medicine, New York, New York, USA.
authors: Kleopatra
authors: K
authors: Rapti
authors: Antoine H
authors: AH
authors: Chaanine
authors: Roger J
authors: RJ
authors: Hajjar
references: Exp Cell Res. 2005 Mar 10;304(1):149-61
references: 15707582
references: Mol Ther. 2010 Jul;18(7):1284-92
references: 20461063
references: J Am Coll Cardiol. 2007 Sep 11;50(11):1038-46
references: 17825712
references: J Virol. 2008 Feb;82(3):1399-406
references: 18045941
references: Gene Ther. 1998 May;5(5):630-4
references: 9797867
references: Nat Med. 2007 Apr;13(4):419-22
references: 17369837
references: Virology. 2004 Dec 20;330(2):375-83
references: 15567432
references: Mol Cell Biol. 2002 Apr;22(8):2821-9
references: 11909974
references: Science. 1965 Aug 13;149(3685):754-6
references: 14325163
references: Interact Cardiovasc Thorac Surg. 2008 Oct;7(5):767-70
references: 18577527
references: Circulation. 2005 Sep 20;112(12):1813-24
references: 16172288
references: Mol Ther. 2009 Jun;17(6):1109-15
references: 19352324
references: Gene Ther. 2005 Oct;12 Suppl 1:S18-27
references: 16231052
references: J Cardiovasc Med (Hagerstown). 2010 Dec;11(12):893-905
references: 20414119
references: J Gene Med. 2008 Jul;10(7):717-33
references: 18452237
references: Nat Med. 2000 Dec;6(12):1395-8
references: 11100126
references: J Am Coll Cardiol. 2009 Jul 7;54(2):160-5
references: 19573734
references: Hum Gene Ther. 2008 Dec;19(12):1359-68
references: 18795839
references: Drug Metab Dispos. 2005 Aug;33(8):1101-7
references: 15879496
references: Heart. 2011 Feb;97(3):181-9
references: 20884790
references: Mol Ther. 2009 Mar;17(3):409-16
references: 19107117
references: J Card Fail. 2002 Dec;8(6 Suppl):S432-49
references: 12555156
references: Curr Opin Biotechnol. 1999 Oct;10(5):440-7
references: 10508634
references: J Immunol. 2009 May 15;182(10):6051-60
references: 19414756
references: Lancet. 2009 Nov 7;374(9701):1597-605
references: 19854499
references: Mol Ther. 2008 Oct;16(10):1703-9
references: 18728640
references: Mayo Clin Proc. 2010 Feb;85(2):180-95
references: 20118395
references: Circ Res. 2005 Sep 2;97(5):488-95
references: 16081870
references: J Thorac Cardiovasc Surg. 2000 Sep;120(3):581-8
references: 10962422
references: Cardiovasc Res. 2008 Apr 1;78(1):18-25
references: 18079102
references: J Infect Dis. 2009 Feb 1;199(3):381-90
references: 19133809
references: Pflugers Arch. 2008 Feb;455(5):767-74
references: 17874127
references: Circulation. 2006 Jul 4;114(1 Suppl):I206-13
references: 16820573
references: Mol Ther. 2009 Aug;17(8):1427-33
references: 19471246
references: Basic Res Cardiol. 2002 Sep;97(5):348-58
references: 12200634
references: Mol Ther. 2004 Oct;10(4):671-8
references: 15451451
references: Proc Natl Acad Sci U S A. 1966 Jun;55(6):1467-74
references: 5227666
references: Stem Cells Dev. 2010 Feb;19(2):229-38
references: 19558219
references: Mol Genet Metab. 2009 Apr;96(4):151-7
references: 19211285
references: Hypertension. 2004 Aug;44(2):203-9
references: 15238569
references: Circulation. 2001 Jul 10;104(2):131-3
references: 11447073
references: J Am Coll Cardiol. 2008 Mar 18;51(11):1112-9
references: 18342232
references: Mol Cell Biochem. 2010 Jun;339(1-2):107-18
references: 20058054
references: Curr Gene Ther. 2009 Dec;9(6):459-74
references: 20021330
references: Mol Ther. 2008 Mar;16(3):571-9
references: 18253156
references: J Thorac Cardiovasc Surg. 2005 Nov;130(5):1364
references: 16256790
references: J Cell Biochem. 2008 Sep 1;105(1):17-24
references: 18500727
references: Mol Ther. 2003 Aug;8(2):306-13
references: 12907153
references: J Control Release. 2003 Dec 5;93(2):213-7
references: 14636726
references: Mol Ther. 2009 Jan;17(1):73-80
references: 18941441
references: Am J Physiol. 1996 Dec;271(6 Pt 2):H2735-9
references: 8997338
references: Mol Ther. 2008 May;16(5):972-978
references: 28178491
references: Circ Res. 2006 Aug 18;99(4):e3-9
references: 16873720
references: Proc Natl Acad Sci U S A. 1994 May 10;91(10):4407-11
references: 8183921
references: Am J Physiol Heart Circ Physiol. 2006 Oct;291(4):H1773-9
references: 16766633
references: Expert Opin Biol Ther. 2008 Jul;8(7):911-22
references: 18549322
references: Mol Med. 2010 May-Jun;16(5-6):222-9
references: 20454523
references: Hum Gene Ther. 2010 Jun;21(6):704-12
references: 20095819
references: Gene Ther. 2008 Jun;15(11):808-16
references: 18385765
references: Mol Ther. 2001 Oct;4(4):383-91
references: 11592843
references: Adv Genet. 2005;53PA:1-18
references: 16243058
references: Physiol Rev. 2008 Oct;88(4):1567-651
references: 18923190
references: J Pharmacol Toxicol Methods. 2007 Jul-Aug;56(1):1-10
references: 17391988
references: Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16363-8
references: 19706466
references: Clin Transl Sci. 2009 Apr;2(2):118-26
references: 20161095
references: Nat Med. 2003 Oct;9(10):1306-12
references: 14502277
references: Circulation. 2003 May 13;107(18):2375-82
references: 12695294
references: Nat Med. 1999 Jan;5(1):78-82
references: 9883843
references: Circulation. 1994 Nov;90(5):2414-24
references: 7525108
references: Circulation. 1999 Dec 7;100(23):2308-11
references: 10587333
references: Circulation. 2009 Mar 10;119(9):1241-52
references: 19237664
references: Transplantation. 2006 Jan 27;81(2):240-6
references: 16436968
references: Gene Ther. 2000 Feb;7(3):232-40
references: 10694800
references: Gene Ther. 2006 Jul;13(13):998-9
references: 17262905
references: Curr Gene Ther. 2005 Aug;5(4):387-98
references: 16101513
references: J Virol. 1999 Nov;73(11):9468-77
references: 10516055
references: Proc Natl Acad Sci U S A. 1982 Mar;79(6):2077-81
references: 6281795
references: Adv Genet. 2009;67:29-60
references: 19914449
references: Gene Ther. 2010 Aug;17(8):980-90
references: 20393510
references: Genet Vaccines Ther. 2008 Sep 23;6:13
references: 18811960
references: Pharmacology. 2000 Sep;61(3):167-73
references: 10971202
references: Gene Ther. 2008 Jun;15(11):870-5
references: 18432276
references: Cardiovasc Res. 2008 Apr 1;78(1):1-2
references: 18250142
references: Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11854-9
references: 12192090
references: Circulation. 2006 Feb 21;113(7):1005-14
references: 16476845
references: Nat Med. 2000 May;6(5):599-602
references: 10802720
references: Gene Ther. 2011 Jan;18(1):43-52
references: 20703310
references: Trends Cardiovasc Med. 2007 Oct;17(7):215-21
references: 17936202
references: Mol Ther. 2006 Sep;14(3):452-5
references: 16822719
references: Methods Mol Biol. 2009;542:87-104
references: 19565897
references: J Gene Med. 2004 Feb;6 Suppl 1:S164-71
references: 14978759
references: Mol Ther. 2010 May;18(5):977-82
references: 20234342
references: Br J Pharmacol. 2003 Oct;140(4):637-46
references: 14534147
references: Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5251-6
references: 9560262
references: Ann N Y Acad Sci. 2006 Oct;1080:426-36
references: 17132799
references: Mol Ther. 2009 Sep;17(9):1492-503
references: 19584819
references: J Gene Med. 2008 Jan;10(1):33-41
references: 18044793
references: Gene Ther. 2003 Apr;10(8):630-6
references: 12692591
references: Circulation. 2003 Jun 3;107(21):2677-83
references: 12742981
references: Am J Physiol Heart Circ Physiol. 2005 Jun;288(6):H2995-3000
references: 15897329
references: Circulation. 2002 Oct 1;106(14):1756-9
references: 12356625
references: Gene Ther. 2002 Dec;9(24):1647-52
references: 12457277
references: Physiol Genomics. 2006 Mar 13;25(1):29-38
references: 16390873
references: Nat Clin Pract Cardiovasc Med. 2008 Sep;5(9):554-65
references: 18665137
references: Gene Ther. 2001 Dec;8(24):1833-9
references: 11821936
references: Circulation. 2002 Feb 26;105(8):904-7
references: 11864915
references: Proc Natl Acad Sci U S A. 1984 Oct;81(20):6466-70
references: 6093102
references: Curr Gene Ther. 2007 Oct;7(5):347-60
references: 17979681
references: J Virol. 2005 Jan;79(1):609-14
references: 15596854
references: J Biol Chem. 2001 Jun 22;276(25):23018-27
references: 11304530
references: J Virol. 2006 Jan;80(1):27-37
references: 16352528
references: Br J Pharmacol. 2010 Jun;160(4):821-32
references: 20590581
references: Cell Reprogram. 2010 Apr;12(2):117-25
references: 20677926
references: Microbiol Mol Biol Rev. 1999 Sep;63(3):725-34
references: 10477314
references: Mol Ther. 2007 Feb;15(2):320-9
references: 17235310
references: Expert Rev Cardiovasc Ther. 2007 Jan;5(1):119-24
references: 17187463
references: Circ Res. 2008 Apr 11;102(7):786-94
references: 18292599
references: J Mol Cell Cardiol. 2011 Feb;50(2):327-32
references: 21040726
references: Heart Fail Rev. 2009 Dec;14(4):225-41
references: 19110970
references: Annu Rev Genet. 2004;38:819-45
references: 15568995
references: Acta Cardiol. 2010 Oct;65(5):565-70
references: 21125979
references: J Virol. 1999 Jan;73(1):576-84
references: 9847362
references: Mol Imaging. 2004 Apr;3(2):69-75
references: 15296671
references: J Virol. 2006 Oct;80(19):9831-6
references: 16973587
references: Circ Res. 2009 Sep 25;105(7):648-56
references: 19696409
references: Nat Rev Cardiol. 2010 Dec;7(12):700-10
references: 20956984
references: FASEB J. 2006 Jan;20(1):136-8
references: 16254044
references: Proc Natl Acad Sci U S A. 1999 May 25;96(11):6400-5
references: 10339599
references: Gene Ther. 2003 Jun;10(11):955-63
references: 12756416
references: J Virol. 2006 May;80(10):5082-5
references: 16641301
references: J Am Coll Cardiol. 2000 Apr;35(5):1323-30
references: 10758976
references: Gene Ther. 2009 Mar;16(3):311-9
references: 19052631
references: Mol Ther. 2008 Dec;16(12):1944-52
references: 18827804
references: J Mol Med (Berl). 2009 May;87(5):455-63
references: 19229505
references: J Virol. 1998 Oct;72(10):8150-7
references: 9733856
references: Mol Biotechnol. 2007 Jun;36(2):151-8
references: 17914194
references: BioDrugs. 2008;22(4):209-22
references: 18611064
references: PLoS One. 2010 Apr 01;5(4):e9943
references: 20376342
references: Virology. 2006 Sep 15;353(1):68-82
references: 16806384
references: Methods Mol Biol. 2003;229:43-55
references: 12824620
references: Circ J. 2009 Feb;73(2):195-200
references: 19106458
references: Circ Res. 2009 Apr 24;104(8):1012-20
references: 19299645
references: J Virol. 2007 Jul;81(14):7540-7
references: 17475652
references: Circulation. 2009 Jan 27;119(3):480-6
references: 19171871
references: Mol Ther. 2010 Apr;18(4):766-74
references: 20068550
references: Gene Ther. 2005 Jun;12(12):958-64
references: 15789062
references: Hum Gene Ther. 2011 Jan;22(1):3-17
references: 21062128
references: J Gene Med. 2003 Nov;5(11):921-8
references: 14601129
references: Gene Ther. 2006 Nov;13(21):1503-11
references: 16791287
references: Nat Med. 1999 Jan;5(1):71-7
references: 9883842
references: J Virol. 2001 Aug;75(15):6884-93
references: 11435568
references: J Card Fail. 2009 Apr;15(3):171-81
references: 19327618
references: Mol Ther. 2005 Aug;12(2):299-306
references: 16043099
references: Gene Ther. 1999 Sep;6(9):1574-83
references: 10490767
references: Gene Ther. 2008 Jan;15(1):12-7
references: 17943147
references: Circulation. 2003 Oct 21;108(16):1933-8
references: 14504183
references: Nat Biotechnol. 2005 Nov;23(11):1435-9
references: 16244658
references: J Mol Cell Cardiol. 2009 Sep;47(3):365-71
references: 19481088
references: Eur J Cardiothorac Surg. 2004 Dec;26(6):1161-8
references: 15541978
references: Cardiovasc Res. 2007 Apr 1;74(1):39-45
references: 17336953
references: Curr Opin Mol Ther. 2009 Oct;11(5):493-503
references: 19806497
references: Heart. 2008 Jan;94(1):89-99
references: 18083952
references: Can J Cardiol. 2007 Sep;23(11):891-8
references: 17876381
references: J Pharmacol Sci. 2006;100(5):323-37
references: 16612046
references: Lancet Neurol. 2003 May;2(5):299-310
references: 12849184
references: Expert Rev Mol Diagn. 2003 Sep;3(5):617-33
references: 14510182
references: Gene Ther. 2001 Oct;8(19):1456-63
references: 11593358
references: Hellenic J Cardiol. 2007 Jan-Feb;48(1):30-6
references: 17388107
references: Science. 1993 May 28;260(5112):1273-9
references: 8493571
references: J Virol. 2004 Jun;78(12):6381-8
references: 15163731
references: Expert Opin Biol Ther. 2010 Jan;10(1):29-41
references: 20078230
references: Mol Ther. 2006 Mar;13(3):506-16
references: 16368273
references: Circulation. 2002 Mar 19;105(11):1291-7
references: 11901038
references: Circ Res. 2007 Jun 22;100(12):1741-8
references: 17495221
references: Hum Gene Ther. 2000 Jan 20;11(2):263-70
references: 10680840
references: Clin Cardiol. 1999 Jan;22(1 Suppl 1):I23-9
references: 9929764
references: Stem Cells Cloning. 2010 Jan 1;3:29-37
references: 21165156
references: Circ Res. 2005 Jan 7;96(1):110-8
references: 15576649
references: Nat Biotechnol. 2010 Jan;28(1):79-82
references: 20037580
references: Eur J Heart Fail. 2009 Nov;11(11):1023-30
references: 19875403
references: Gene Ther. 2005 Oct;12(20):1509-16
references: 15858608
references: Mol Genet Metab. 2009 May;97(1):4-5
references: 19285443
references: Trends Mol Med. 2005 May;11(5):240-50
references: 15882612
references: Gene Ther. 2008 Dec;15(23):1558-65
references: 18615116
references: Curr Opin Hematol. 2008 May;15(3):215-20
references: 18391788
references: Cardiovasc Res. 2008 Jan 15;77(2):285-92
references: 18006483
references: Methods Mol Biol. 2008;433:259-75
references: 18679629
references: Methods Mol Med. 2005;108:315-28
references: 16028692
references: J Am Coll Cardiol. 2007 Jul 17;50(3):253-60
references: 17631218
references: Cardiovasc Res. 2005 Jun 1;66(3):512-9
references: 15914116
references: Gene Ther. 2008 Feb;15(3):161-70
references: 18033312
references: J Thorac Cardiovasc Surg. 2008 Mar;135(3):673-8
references: 18329492
references: Gene Ther. 2010 Mar;17(3):295-304
references: 19907498
references: Circulation. 2002 Jan 29;105(4):502-8
references: 11815435
references: Gene Ther. 2007 Jul;14(13):989-97
references: 17251988
references: Br J Haematol. 2005 Feb;128(3):303-9
references: 15667531
references: Gene Ther. 2006 Nov;13(21):1495-502
references: 16775632
references: Mol Ther. 2007 Apr;15(4):649-50
references: 17372595
references: Am J Physiol Heart Circ Physiol. 2004 Jul;287(1):H172-7
references: 15001445
references: Lancet. 1996 Aug 10;348(9024):370-4
references: 8709735
references: Gene Ther. 1999 Apr;6(4):683-8
references: 10476229
references: Circulation. 2005 Aug 30;112(9 Suppl):I157-65
references: 16159809
references: J Card Fail. 2007 Jun;13(5):401-14
references: 17602988
references: Nature. 1996 Apr 4;380(6573):435-9
references: 8602241
references: Mol Ther. 2008 Oct;16(10):1648-56
references: 18682697
references: Mol Ther. 2004 Dec;10(6):981-9
references: 15564130
references: Nat Biotechnol. 2005 Mar;23(3):321-8
references: 15735640
references: Mol Ther. 2010 Aug;18(8):1458-61
references: 20531394
references: J Orthop Res. 2009 Apr;27(4):421-6
references: 18973234
references: J Virol. 1997 Feb;71(2):941-8
references: 8995611
references: Mol Ther. 2009 Feb;17(2):262-8
references: 19002160
references: Circulation. 2007 May 15;115(19):2506-15
references: 17470693
references: J Cardiovasc Transl Res. 2010 Dec;3(6):674-82
references: 20842469
references: Curr Gene Ther. 2007 Oct;7(5):316-24
references: 17979678
references: N Engl J Med. 1990 Aug 30;323(9):570-8
references: 2381442
references: Science. 2007 Jul 27;317(5837):477
references: 17656716
references: Trends Cardiovasc Med. 2008 May;18(4):133-41
references: 18555186
references: Curr Opin Mol Ther. 2006 Aug;8(4):295-300
references: 16955692
references: Cardiovasc Res. 2006 Apr 1;70(1):70-8
references: 16448634
references: Blood. 2009 Jan 22;113(4):797-806
references: 18957684
references: J Virol. 2003 Apr;77(8):4751-9
references: 12663782
references: Nat Med. 2003 Sep;9(9):1195-201
references: 12910262
references: Exp Cell Res. 2009 Dec 10;315(20):3521-31
references: 19800880
references: Hypertension. 2002 Feb;39(2 Pt 2):651-5
references: 11882625
references: Stem Cells. 2007 Aug;25(8):2118-27
references: 17478584
references: Gene Ther. 2009 May;16(5):629-34
references: 19212427
references: J Gen Virol. 2009 Nov;90(Pt 11):2622-2633
references: 19641045
references: J Am Coll Cardiol. 2000 Mar 15;35(4):1031-9
references: 10732905
references: Cardiovasc Res. 2006 Jan;69(1):46-56
references: 16288730
references: Ther Adv Cardiovasc Dis. 2009 Jun;3(3):215-29
references: 19443513
references: Hum Gene Ther. 2004 Oct;15(10):989-94
references: 15585114
references: Hum Gene Ther. 2010 Apr;21(4):371-80
references: 19947886
references: Hum Gene Ther. 2006 Jan;17(1):10-9
references: 16409121
references: Circulation. 2001 Sep 18;104(12):1424-9
references: 11560860
references: J Card Fail. 2008 Jun;14(5):355-67
references: 18514926
references: J Heart Lung Transplant. 2008 Aug;27(8):830-4
references: 18656794
references: Mol Ther. 2006 Sep;14(3):316-27
references: 16824801
references: Am J Physiol Heart Circ Physiol. 2007 Feb;292(2):H1204-7
references: 17012346
references: J Virol. 2002 Jan;76(2):791-801
references: 11752169
references: Am J Pathol. 2007 Jul;171(1):162-71
references: 17591963
references: Am J Epidemiol. 1968 Nov;88(3):368-78
references: 4301609
references: J Mol Cell Cardiol. 2001 May;33(5):1005-15
references: 11343422
references: Eur J Cardiothorac Surg. 2009 Oct;36(4):644-50
references: 19524448
references: FASEB J. 2003 Jan;17(1):61-3
references: 12424227
references: Mol Ther. 2010 Mar;18(3):570-8
references: 20040913
references: Eur J Cardiothorac Surg. 2002 May;21(5):847-52
references: 12062273
references: Mol Ther. 2008 Dec;16(12):1953-1959
references: 28189009
references: J Virol. 2003 Dec;77(24):13062-72
references: 14645563
references: Circ J. 2006 Nov;70(11):1503-8
references: 17062978
references: J Cardiovasc Pharmacol Ther. 2004 Dec;9(4):243-55
references: 15678243
references: Curr Opin Nephrol Hypertens. 1996 Jan;5(1):35-44
references: 8834160
references: J Am Coll Cardiol. 2004 Sep 1;44(5):1124-9
references: 15337228
references: Cardiovasc Res. 1997 Sep;35(3):560-6
references: 9415302
references: Circ Res. 2009 Oct 9;105(8):724-36
references: 19815827
references: Circ Res. 2005 Apr 15;96(7):756-66
references: 15746443
references: Eur Heart J. 2011 Aug;32(16):2075-84
references: 21196445
references: Circulation. 2000 Jan 4-11;101(1):71-7
references: 10618307
references: Cardiovasc Res. 2007 Feb 1;73(3):453-62
references: 17097076
references: Science. 1994 Apr 22;264(5158):582-6
references: 8160017
references: Circulation. 1998 Feb 24;97(7):645-50
references: 9495299
references: Circ Res. 2004 Jul 9;95(1):9-20
references: 15242981
references: Mol Ther. 2006 Jul;14(1):34-44
references: 16682254
references: Eur J Pharmacol. 2004 Apr 12;489(3):167-77
references: 15087239
references: Transplantation. 2004 Jun 15;77(11):1748-54
references: 15201677
references: Cardiovasc Res. 2003 Dec 1;60(3):478-87
references: 14659793
references: Mol Ther. 2008 Jun;16(6):1026-32
references: 18388909
references: Mol Ther. 2008 Jun;16(6):1073-80
references: 18414476
references: J Virol. 2001 Jun;75(11):5222-9
references: 11333904
references: Mol Ther. 2008 Jul;16(7):1252-1260
references: 28178482
references: Circulation. 1998 Dec 22-29;98(25):2800-4
references: 9860779
references: Am J Physiol. 1997 Jan;272(1 Pt 2):H310-7
references: 9038951
references: Methods Mol Biol. 2008;437:51-91
references: 18369962
references: Curr Gene Ther. 2005 Jun;5(3):299-310
references: 15975007
references: Physiol Rev. 2007 Apr;87(2):521-44
references: 17429040
references: Cardiovasc Res. 2011 Jan 1;89(1):20-30
references: 20851808
references: Hum Gene Ther. 2001 Sep 1;12(13):1601-10
references: 11535164
references: Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3946-51
references: 19234115
references: Circ Heart Fail. 2009 May;2(3):262-71
references: 19808348
references: Mol Ther. 2008 Oct;16(10):1719-26
references: 18665157
references: J Virol. 2007 Oct;81(20):11304-21
references: 17686847
references: Catheter Cardiovasc Interv. 2002 Mar;55(3):392-7
references: 11870950
references: Pediatr Cardiol. 2009 Jul;30(5):710-5
references: 19340478
references: Am J Physiol. 1999 May;276(5):C1148-53
references: 10329964
references: Mol Ther. 2007 Dec;15(12):2154-63
references: 17895861
references: Mol Biotechnol. 2007 May;36(1):71-80
references: 17827541
references: Chin Med J (Engl). 2010 Jul;123(13):1702-8
references: 20819633
references: Circulation. 2003 Dec 2;108(22):2790-7
references: 14638552