Development of novel cardiovascular therapeutics from small regulatory RNA molecules - an outline of key requirements

Current Pharmaceutical Design

Volumn 16, Issue 20, 2010, Pages 2252-2268

  Poller, W ^a   Fechner, H ^a,b  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b TECHNISCHE UNIVERSITÄT BERLIN   (Germany)

Author keywords

Gene therapy; microRNAs; regulatory RNAs; RNA drugs; RNA interference

Indexed keywords

DOUBLE STRANDED RNA; MICRORNA;

ARTICLE; GENE THERAPY; HEART FAILURE; NONHUMAN; PRIORITY JOURNAL; REGULATORY RNA SEQUENCE; RNA INTERFERENCE; RNA SYNTHESIS;

ANIMALS; CARDIOVASCULAR DISEASES; DRUG DESIGN; GENE EXPRESSION REGULATION; GENE THERAPY; HUMANS; MICRORNAS; PHARMACOGENETICS; RNA, SMALL INTERFERING;

EID: 77955603961     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161210791792813     Document Type: Article

References (136)

1. Erdmann V, Poller W, Barciszewksi J. RNA Technologies in Cardiovascular Medicine and Research - Status and Challenges. Heidelberg - New York: Springer 2008.
2. van Rooij E, Sutherland LB, Liu N, et al. A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc Natl Acad Sci USA 2006; 103(48): 18255- 60.
3. Thum T, Galuppo P, Wolf C, et al. MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure. Circulation 2007; 116: 258-67.
4. Thum T, Catalucci D, Bauersachs J. MicroRNAs: novel regulators in cardiac development and disease. Cardiovasc Res 2008; 79(4): 562-70.
5. Bonauer A, Carmona G, Iwasaki M, et al. MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science 2009; 324(5935): 1710-3.
6. van Rooij E, Olson EN. Searching for miR-acles in cardiac fibrosis. Circ Res 2009; 104(2): 138-40.
7. Fire A, Xu S, Montgomery M, et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 1998; 391: 806-11.
8. Elbashir S, Harborth J, Lendeckel W, et al. Duplexes of 21- nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 2001; 411: 494-8.
9. Thum T, Gross C, Fiedler J, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 2008; 456(7224): 980-4.
10. Lee Y, Kim M, Han J, et al. MicroRNA genes are transcribed by RNA polymerase II. EMBO J 2004; 23(20): 4051-60.
11. Cullen BR. Transcription and processing of human microRNA precursors. Mol Cell 2004; 16(6): 861-5.
12. Gregory RI, Chendrimada TP, Shiekhattar R. MicroRNA biogenesis: isolation and characterization of the microprocessor complex. Methods Mol Biol 2006; 342: 33-47.
13. Gregory RI, Chendrimada TP, Cooch N, et al. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell 2005; 123(4): 631-40.
14. Yi R, Qin Y, Macara IG, et al. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev 2003; 17(24): 3011-6.
15. Yi R, Doehle BP, Qin Y, et al. Overexpression of exportin 5 enhances RNA interference mediated by short hairpin RNAs and microRNAs. RNA 2005; 11(2): 220-6.
16. Sontheimer EJ. Assembly and function of RNA silencing complexes. Nat Rev Mol Cell Biol 2005; 6(2): 127-38.
17. Lim LP, Lau NC, Garrett-Engele P, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 2005; 433(7027): 769-73.
18. Selbach M, Schwanhausser B, Thierfelder N, et al. Widespread changes in protein synthesis induced by microRNAs. Nature 2008; 455(7209): 58-63.
19. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009; 136(2): 215-33.
20. Hendrickson DG, Hogan DJ, McCullough HL, et al. Concordant regulation of translation and mRNA abundance for hundreds of targets of a human microRNA. PLoS Biol 2009; 7(11): e1000238.
21. Fechner H, Kurreck J. Vector-mediated and viral delivery of short hairpin RNAs. Therapeutic Oligonucleotides. Cambridge: Royal Society of Chemistry Publishing 2008; pp. 267-95.
22. Liu J, Carmell MA, Rivas FV, et al. Argonaute2 is the catalytic engine of mammalian RNAi. Science 2004; 305(5689): 1437-41.
23. Krutzfeldt J, Rajewsky N, Braich R, et al. Silencing of microRNAs in vivo with 'antagomirs'. Nature 2005; 438(7068): 685-9.
24. Lu Y, Xiao J, Lin H, et al. A single anti-microRNA antisense oligodeoxyribonucleotide (AMO) targeting multiple microRNAs offers an improved approach for microRNA interference. Nucleic Acids Res 2009; 37(3): e24.
25. Xiao J, Yang B, Lin H, et al. Novel approaches for gene-specific interference via manipulating actions of microRNAs: examination on the pacemaker channel genes HCN2 and HCN4. J Cell Physiol 2007; 212(2): 285-92.
26. Ebert MS, Neilson JR, Sharp PA. MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 2007; 4(9): 721-6.
27. Sayed D, Rane S, Lypowy J, et al. MicroRNA-21 targets Sprouty2 and promotes cellular outgrowths. Mol Biol Cell 2008; 19(8): 3272-82.
28. Suckau L, Fechner H, Chemaly E, et al. Chronic cardiac-targeted RNA interference for the treatment of heart failure restores cardiac function and reduces pathological hypertrophy. Circulation 2009; 119: 1241-52.
29. Merl S, Michaelis C, Jaschke B, et al. Targeting 2A protease by RNA interference attenuates coxsackieviral cytopathogenicity and promotes survival in highly susceptible mice. Circulation 2005; 111(13): 1583-92.
30. Sorensen DR, Leirdal M, Sioud M. Gene silencing by systemic delivery of synthetic siRNAs in adult mice. J Mol Biol 2003; 327(4): 761-6.
31. Watanabe A, Arai M, Yamazaki M, et al. Phospholamban ablation by RNA interference increases Ca2+ uptake into rat cardiac myocyte sarcoplasmic reticulum. J Mol Cell Cardiol 2004; 37(3): 691- 8.
32. Grimm D, Kay MA. Therapeutic short hairpin RNA expression in the liver: viral targets and vectors. Gene Ther 2006; 13(6): 563-75.
33. Grimm D, Streetz KL, Jopling CL, et al. Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 2006; 441(7092): 537-41.
34. Fechner H, Suckau L, Kurreck J, et al. Highly efficient and specific modulation of cardiac calcium homeostasis by adenovector-derived short hairpin RNA targeting phospholamban. Gene Therapy 2007; 14: 211-8.
35. Andino LM, Takeda M, Kasahara H, et al. AAV-mediated knockdown of phospholamban leads to improved contractility and calcium handling in cardiomyocytes. J Gene Med 2008; 10(2): 132-42.
36. Fechner H, Sipo I, Westermann D, et al. Cardiac-targeted RNA interference mediated by an AAV9 vector improves cardiac function in coxsackievirus B3 cardiomyopathy. J Mol Med 2008; 86(9): 987-97.
37. v-integrin does not correlate with adenovector targeting in vivo indicating anatomical vector barriers. Gene Therapy 1999; 6(9): 1520-35.
38. Gupta S, Maitra R, Young D, et al. Silencing the myotrophin gene by RNA interference leads to the regression of cardiac hypertrophy. Am J Physiol Heart Circ Physiol 2009; 297(2): H627-36.
39. Hajjar R, Schmidt U, Matsui T, et al. Modulation of ventricular function through gene transfer in vivo. Proc Natl Acad Sci USA 1998; 95: 5251-6.
40. 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 2002; 8(8): 864-71.
41. Ikeda Y, Gu Y, Iwanaga Y, et al. Restoration of deficient membrane proteins in the cardiomyopathic hamster by in vivo cardiac gene transfer. Circulation 2002; 105: 502-8.
42. Grimm D, Kleinschmidt JA. Progress in adeno-associated virus type 2 vector production: promises and prospects for clinical use. Hum Gene Ther 1999; 10(15): 2445-50.
43. Hacein-Bey-Abina S, vonKalle C, Schmidt M, et al. A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. New Engl J Med 2003; 348(3): 255-6.
44. Kaspar BK, Roth DM, Lai NC, et al. Myocardial gene transfer and long-term expression following intracoronary delivery of adenoassociated virus. J Gene Med 2005; 7(3): 316-24.
45. Bankiewicz KS, Forsayeth J, Eberling JL, et al. Long-term clinical improvement in MPTP-lesioned primates after gene therapy with AAV-hAADC. Mol Ther 2006; 14(4): 564-70.
46. Nakai H, Thomas CE, Storm TA, et al. A limited number of transducible hepatocytes restricts a wide-range linear vector dose response in recombinant adeno-associated virus-mediated liver transduction. J Virol 2002; 76(22): 11343-9.
47. Gao GP, Alvira MR, Wang L, et al. Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. Proc Natl Acad Sci USA 2002; 99(18): 11854-9.
48. Gao GP, Lu Y, Sun X, et al. High-level transgene expression in nonhuman primate liver with novel adeno-associated virus serotypes containing self-complementary genomes. J Virol 2006; 80(12): 6192-4.
49. Bish LT, Morine K, Sleeper MM, et al. Adeno-associated virus (AAV) serotype 9 provides global cardiac gene transfer superior to AAV1, AAV6, AAV7, and AAV8 in the mouse and rat. Hum Gene Ther 2008; 19(12): 1359-68.
50. 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 2006; 14(1): 45-53.
51. Pačak CA, Mah CS, Thattaliyath BD, et al. Recombinant adenoassociated virus serotype 9 leads to preferential cardiac transduction in vivo. Circ Res 2006; 99(4): e3-9.
52. Yang L, Jiang J, Drouin LM, et al. A myocardium tropic adenoassociated virus (AAV) evolved by DNA shuffling and in vivo selection. Proc Natl Acad Sci USA 2009; 106(10): 3946-51.
53. Lipskaia L, Chemaly ER, Hadri L, et al. Sarcoplasmic reticulum Ca(2+) ATPase as a therapeutic target for heart failure. Expert Opin Biol Ther 2010; 10(1): 29-41.
54. 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 2009; 15(3): 171-81.
55. Goehringer C, Rutschow D, Bauer R, et al. Prevention of cardiomyopathy in delta-sarcoglycan knockout mice after systemic transfer of targeted adeno-associated viral vectors. Cardiovasc Res 2009; 82(3): 404-10.
56. Muller OJ, Leuchs B, Pleger ST, et al. Improved cardiac gene transfer by transcriptional and transductional targeting of adenoassociated viral vectors. Cardiovasc Res 2006; 70(1): 70-8.
57. Zeng Y, Wagner EJ, Cullen BR. Both natural and designed micro RNAs can inhibit the expression of cognate mRNAs when expressed in human cells. Mol Cell 2002; 9(6): 1327-33.
58. Liu YP, Haasnoot J, ter Brake O, et al. Inhibition of HIV-1 by multiple siRNAs expressed from a single microRNA polycistron. Nucleic Acids Res 2008; 36(9): 2811-24.
59. Zhao Y, Samal E, Srivastava D. Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature 2005; 436(7048): 214-20.
60. Rhee SW, Stimers JR, Wang W, et al. Vascular smooth musclespecific knockdown of the noncardiac form of the L-type calcium channel by microRNA-based short hairpin RNA as a potential antihypertensive therapy. J Pharmacol Exp Ther 2009; 329(2): 775-82.
61. Brown BD, Venneri MA, Zingale A, et al. Endogenous microRNA regulation suppresses transgene expression in hematopoietic lineages and enables stable gene transfer. Nat Med 2006; 12(5): 585-91.
62. Kelly EJ, Russell SJ. MicroRNAs and the regulation of vector tropism. Mol Ther 2009; 17(3): 409-16.
63. Kelly EJ, Hadac EM, Greiner S, et al. Engineering microRNA responsiveness to decrease virus pathogenicity. Nat Med 2008; 14(11): 1278-83.
64. Leja J, Nilsson B, Yu D, et al. Double-detargeted oncolytic adenovirus shows replication arrest in liver cells and retains neuroendocrine cell killing ability. PLoS One 2010; 5(1): e8916.
65. Cawood R, Chen HH, Carroll F, et al. Use of tissue-specific microRNA to control pathology of wild-type adenovirus without attenuation of its ability to kill cancer cells. PLoS Pathog 2009; 5(5): e1000440.
66. Suzuki T, Sakurai F, Nakamura S, et al. miR-122a-regulated expression of a suicide gene prevents hepatotoxicity without altering antitumor effects in suicide gene therapy. Mol Ther 2008; 16(10): 1719-26.
67. Brown BD, Naldini L. Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications. Nat Rev Genet 2009; 10(8): 578-85.
68. Hoshijima M, Knoll R, Pashmforoush M, et al. Reversal of calcium cycling defects in advanced heart failure toward molecular therapy. J Am Coll Cardiol 2006; 48(9 Suppl): A15-23.
69. Takahashi H, Hirai Y, Migita M, et al. Long-term systemic therapy of Fabry disease in a knockout mouse by adeno-associated virusmediated muscle-directed gene transfer. Proc Natl Acad Sci USA 2002; 99(21): 13777-82.
70. Kawada T, Nakazawa M, Nakauchi S, et al. Rescue of hereditary form of dilated cardiomyopathy by rAAV-mediated somatic gene therapy: Amelioration of morphological findings, sarcolemmal permeability, cardiac performances, and the prognosis of TO-2 hamsters. Proc Natl Acad Sci USA 2002; 99: 901-6.
71. Haghighi K, Kolokathis F, Gramolini AO, et al. A mutation in the human phospholamban gene, deleting arginine 14, results in lethal, hereditary cardiomyopathy. Proc Natl Acad Sci USA 2006; 103(5): 1388-93.
72. van de Wetering M, Oving I, Muncan V, et al. Specific inhibition of gene expression using a stably integrated, inducible smallinterfering- RNA vector. EMBO Rep 2003; 4(6): 609-15.
73. Gupta S, Schoer RA, Egan JE, et al. Inducible, reversible, and stable RNA interference in mammalian cells. Proc Natl Acad Sci USA 2004; 101(7): 1927-32.
74. Wu RH, Cheng TL, Lo SR, et al. A tightly regulated and reversibly inducible siRNA expression system for conditional RNAi-mediated gene silencing in mammalian cells. J Gene Med 2007; 9(7): 620- 34.
75. Miyake K, Flygare J, Kiefer T, et al. Development of cellular models for ribosomal protein S19 (RPS19)-deficient diamond-blackfan anemia using inducible expression of siRNA against RPS19. Mol Ther 2005; 11(4): 627-37.
76. Wiznerowicz M, Szulc J, Trono D. Tuning silence: conditional systems for RNA interference. Nat Methods 2006; 3(9): 682-8.
77. Wiznerowicz M, Trono D. Conditional suppression of cellular genes: lentivirus vector-mediated drug-inducible RNA interference. J Virol 2003; 77(16): 8957-61.
78. Zhou H, Huang C, Xia XG. A tightly regulated Pol III promoter for synthesis of miRNA genes in tandem. Biochim Biophys Acta 2008; 1779(11): 773-9.
79. Hiraoka-Kanie M, Miyagishi M, Yamashita JK. Differentiation stage-specific analysis of gene function with inducible short hairpin RNA in differentiating embryonic stem cells. Biochem Biophys Res Commun 2006; 351(3): 669-74.
80. Amar L, Desclaux M, Faucon-Biguet N, et al. Control of small inhibitory RNA levels and RNA interference by doxycycline induced activation of a minimal RNA polymerase III promoter. Nucleic Acids Res 2006; 34(5): e37.
81. Szulc J, Wiznerowicz M, Sauvain MO, et al. A versatile tool for conditional gene expression and knockdown. Nat Methods 2006; 3(2): 109-16.
82. Chen Y, Stamatoyannopoulos G, Song CZ. Down-regulation of CXCR4 by inducible small interfering RNA inhibits breast cancer cell invasion in vitro. Cancer Res 2003; 63(16): 4801-4.
83. Epanchintsev A, Jung P, Menssen A, et al. Inducible microRNA expression by an all-in-one episomal vector system. Nucleic Acids Res 2006; 34(18): e119.
84. Shin KJ, Wall EA, Zavzavadjian JR, et al. A single lentiviral vector platform for microRNA-based conditional RNA interference and coordinated transgene expression. Proc Natl Acad Sci USA 2006; 103(37): 13759-64.
85. Wiederschain D, Wee S, Chen L, et al. Single-vector inducible lentiviral RNAi system for oncology target validation. Cell Cycle 2009; 8(3): 498-504.
86. Fechner H, Wang X, Srour M, et al. A novel tetracyclinecontrolled transactivator-transrepressor system enables external control of oncolytic adenovirus replication. Gene Therapy 2003; 10: 1680-90.
87. Srour M, Fechner H, Wang X, et al. Regulation of human factor IX expression using a doxycycline-inducible gene expression system. Thromb Haemost 2003; 90: 398-405.
88. Chtarto A, Bender H, Hanemann C, et al. Tetracycline-inducible transgene expression mediated by a single AAV vector. Gene Therapy 2003; 10: 84-94.
89. Sun J, Anand-Jawa V, Chatterjee S, et al. Immune responses to adeno-associated virus and its recombinant vectors. Gene Therapy 2003; 10: 964-76.
90. Li C, Hirsch M, DiPrimio N, et al. Cytotoxic-T-lymphocytemediated elimination of target cells transduced with engineered adeno-associated virus type 2 vector in vivo. J Virol 2009; 83(13): 6817-24.
91. Asokan A, Johnson JS, Li C, et al. Bioluminescent virion shells: new tools for quantitation of AAV vector dynamics in cells and live animals. Gene Ther 2008; 15(24): 1618-22.
92. Pinkert S, Westermann D, Wang X, et al. Prevention of cardiac dysfunction in acute Coxsackievirus B3 cardiomyopathy by inducible expression of a soluble Coxsackievirus-adenovirus-receptor. Circulation 2009; 120(23): 2358-66.
93. Hunt SA, Abraham WT, Chin MH, et al. Yancy CW 2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults. Circulation 2009; 119(14): e391-479.
94. Bursi F, Weston SA, Redfield MM, et al. Systolic and diastolic heart failure in the community. J Am Med Assoc 2006; 296(18): 2209-16.
95. Trulock EP, Christie JD, Edwards LB, et al. Registry of the International Society for Heart and Lung Transplantation: twenty-fourth official adult lung and heart-lung transplantation report-2007. J Heart Lung Transplant 2007; 26(8): 782-95.
96. Hernandez AF, Shea AM, Milano CA, et al. Long-term outcomes and costs of ventricular assist devices among Medicare beneficiaries. JAMA 2008; 300(20): 2398-406.
97. Rosenzweig A. Cardiac cell therapy--mixed results from mixed cells. N Engl J Med 2006; 355(12): 1274-7.
98. Puceat M. Pharmacological approaches to regenerative strategies for the treatment of cardiovascular diseases. Curr Opin Pharmacol 2008; 8(2): 189-92.
99. Kuhn B, del Monte F, Hajjar RJ, et al. Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair. Nat Med 2007; 13(8): 962-9.
100. Shimazaki M, Nakamura K, Kii I, et al. Periostin is essential for cardiac healing after acute myocardial infarction. J Exp Med 2008; 205(2): 295-303.
101. Bock-Marquette I, Saxena A, White MD, et al. Thymosin β4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature 2004; 432(7016): 466-72.
102. Schmidt U, Hajjar RJ, Kim CS, et al. Human heart failure: cAMP stimulation of SR Ca(2+)-ATPase activity and phosphorylation level of phospholamban. Am J Physiol 1999; 277(2 Pt 2): H474-80.
103. MacLennan D, Kranias E. Phospholamban: A crucial regulator of cardiac contractility. Nat Rev Mol Cell Biol 2003; 4: 566-76.
104. 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 2004; 113(5): 727-36.
105. Eizema K, Fechner H, Bezstarosti K, et al. Adenovirus-based phospholamban-antisense-mRNA expression as a novel approach to improve cardiac contractile dysfunction - Comparison of a constitutive viral versus an endothelin-1-responsive cardiac promoter. Circulation 2000; 101: 2193-9.
106. Dieterle T, Meyer M, Gu Y, et al. Gene transfer of a phospholamban- targeted antibody improves calcium handling and cardiac function in heart failure. Cardiovasc Res 2005; 67(4): 678-88.
107. Meyer M, Belke DD, Trost SU, et al. A recombinant antibody increases cardiac contractility by mimicking phospholamban phosphorylation. FASEB J 2004; 18(11): 1312-4.
108. 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 1999; 99(3): 313-22.
109. Wang Z, Zhu T, Qiao C, et al. Adeno-associated virus serotype 8 efficiently delivers genes to muscle and heart. Nat Biotechnol 2005; 23(3): 321-8.
110. Li J, Hu SJ, Sun J, et al. Construction of phospholamban antisense RNA recombinant adeno-associated virus vector and its effects in rat cardiomyocytes. Acta Pharmacol Sin 2005; 26(1): 51-5.
111. Sakata S, Lebeche D, Sakata Y, et al. Transcoronary gene transfer of SERCA2a increases coronary blood flow and decreases cardiomyocyte size in a type 2 diabetic rat model. Am J Physiol Heart Circ Physiol 2007; 292(2): H1204-7.
112. Sakata S, Lebeche D, Sakata N, et al. Restoration of mechanical and energetic function in failing aortic-banded rat hearts by gene transfer of calcium cycling proteins. J Mol Cell Cardiol 2007; 42(4): 852-61.
113. del Monte F, Lebeche D, Guerrero JL, et al. Abrogation of ventricular arrhythmias in a model of ischemia and reperfusion by targeting myocardial calcium cycling. Proc Natl Acad Sci USA 2004; 101(15): 5622-7.
114. Sakata S, Lebeche D, Sakata Y, et al. Mechanical and metabolic rescue in a type II diabetes model of cardiomyopathy by targeted gene transfer. Mol Ther 2006; 13(5): 987-96.
115. Lowes BD, Gilbert EM, Abraham WT, et al. Myocardial gene expression in dilated cardiomyopathy treated with β-blocking agents. N Engl J Med 2002; 346(18): 1357-65.
116. Ding Z, Georgiev P, Thöny B. Administration-route and genderindependent long-term therapeutic correction of phenylketonuria (PKU) in a mouse model by recombinant adeno-associated virus 8 pseudotyped vector-mediated gene transfer. Gene Ther 2006; 13: 587-93.
117. Schmitt J, Kamisago M, Asahi M, et al. Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban. Science 2003; 299: 1410-3.
118. Haghighi K, Kolokathis F, Pater L, et al. Human phospholamban null results in lethal dilated cardiomyopathy revealing a critical difference between mouse and human. J Clin Invest 2003; 111(6): 869-76.
119. Zhao W, Yuan Q, Qian J, et al. The presence of Lys27 instead of Asn27 in human phospholamban promotes sarcoplasmic reticulum Ca2+-ATPase superinhibition and cardiac remodeling. Circulation 2006; 113(7): 995-1004.
120. Yang B, Lin H, Xiao J, et al. The muscle-specific microRNA miR- 1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nat Med 2007; 13(4): 486-91.
121. Wu X, Zhang T, Bossuyt J, et al. Local InsP3-dependent perinuclear Ca2+ signaling in cardiac myocyte excitation-transcription coupling. J Clin Invest 2006; 116: 675-82.
122. Molkentin J. Dichotomy of Ca2+ in the heart: contraction versus intracellular signaling. J Clin Invest 2006; 116: 623-6.
123. Kockskämper J, Seidlmayer L, Walther S, et al. Endothelin-1 enhances nuclear Ca2+ transients in atrial myocytes through Ins(1,4,5)P3-dependent Ca2+ release from perinuclear Ca2+ stores. J Cell Sci 2008; 121: 186-95.
124. Care A, Catalucci D, Felicetti F, et al. MicroRNA-133 controls cardiac hypertrophy. Nat Med 2007; 13(5): 613-8.
125. van Rooij E, Sutherland LB, Qi X, et al. Control of stressdependent cardiac growth and gene expression by a microRNA. Science 2007; 316(5824): 575-9.
126. Li W, Asokan A, Wu Z, et al. Engineering and selection of shuffled AAV genomes: a new strategy for producing targeted biological nanoparticles. Mol Ther 2008; 16(7): 1252-60.
127. Asokan A, Conway JC, Phillips JL, et al. Reengineering a receptor footprint of adeno-associated virus enables selective and systemic gene transfer to muscle. Nat Biotechnol 2010; 28(1): 79-82.
128. Woo YJ, Panlilio CM, Cheng RK, et al. Therapeutic delivery of cyclin A2 induces myocardial regeneration and enhances cardiac function in ischemic heart failure. Circulation 2006; 114(1 Suppl): I206-13.
129. Lam JT, Moretti A, Laugwitz KL. Multipotent progenitor cells in regenerative cardiovascular medicine. Pediatr Cardiol 2009; 30(5): 690-8.
130. Moretti A, Caron L, Nakano A, et al. Multipotent Embryonic Isl1(+) Progenitor Cells Lead to Cardiac, Smooth Muscle, and Endothelial Cell Diversification. Cell 2006; 127(6): 1151-65.
131. Laugwitz KL, Moretti A, Lam J, et al. Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 2005; 433(7026): 647-53.
132. Chien KR, Domian IJ, Parker KK. Cardiogenesis and the complex biology of regenerative cardiovascular medicine. Science 2008; 322(5907): 1494-7.
133. Fazi F, Nervi C. MicroRNA: basic mechanisms and transcriptional regulatory networks for cell fate determination. Cardiovasc Res 2008; 79(4): 553-61.
134. Crosby ME, Devlin CM, Glazer PM, et al. Emerging roles of microRNAs in the molecular responses to hypoxia. Curr Pharm Des 2009; 15(33): 3861-6.
135. Gruchala M, Roy H, Bhardwaj S, et al. Gene therapy for cardiovascular diseases. Curr Pharm Des 2004; 10(4): 407-23.
136. Zaiou M, Benachour H, Marteau JB, et al. Genomics and the prospects of existing and emerging therapeutics for cardiovascular diseases. Curr Pharm Des 2009; 15(27): 3193-206.