International Journal of Gerontology
Volume 2, Issue 2 , Pages 35-47 , June 2008

Nonviral Technologies for Gene Therapy in Cardiovascular Research

  • Cheng-Huang Su

      Affiliations

    • Division of Cardiology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
    • Mackay Medicine, Nursing and Management College, Taipei, Taiwan
    • Corresponding Author InformationCorrespondence to: Dr Cheng-Huang Su, Division of Cardiology, Department of Internal Medicine, Mackay Memorial Hospital, 92, Section 2, Chung-San North Road, Taipei 10449, Taiwan
  • ,
  • Hung-I Yeh

      Affiliations

    • Division of Cardiology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
    • Mackay Medicine, Nursing and Management College, Taipei, Taiwan
    • Taipei Medical University, Taipei, Taiwan
  • ,
  • Charles Jia-Yin Hou

      Affiliations

    • Division of Cardiology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
  • ,
  • Cheng-Ho Tsai

      Affiliations

    • Division of Cardiology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
    • Mackay Medicine, Nursing and Management College, Taipei, Taiwan
    • Taipei Medical University, Taipei, Taiwan

,Accepted 22 April 2008.

References 

  1. Russell SJ . Science, medicine, and the future. Gene therapy . BMJ . 1997;315:1289–1292
  2. Nabel EG , Plautz G , Boyce FM , Stanley JC , Nabel GJ . Recombinant gene expression in vivo within endothelial cells of the arterial wall . Science . 1989;244:1342–1344
  3. Blaese RM , Culver KW , Miller AD , Carter CS , Fleisher T , Clerici M , et al.   T lymphocyte-directed gene therapy for ADA-SCID: initial trial results after 4 years . Science . 1995;270:475–480
  4. The Journal of Gene Medicine Clinical Trial Web site . http://www.wiley.co.uk/genetherapy/clinical/ Updated: March 2008. [Accessed: April 2008]
  5. Rajagopalan S , Mohler E , Lederman RJ , Saucedo J , Mendelsohn FO , Olin J , et al.   Regional Angiogenesis with Vascular Endothelial Growth Factor (VEGF) in peripheral arterial disease: design of the RAVE trial . Am Heart J . 2003;145:1114–1118
  6. Rissanen TT , Markkanen JE , Arve K , Rutanen J , Kettunen MI , Vajanto I , et al.   Fibroblast growth factor 4 induces vascular permeability, angiogenesis and arteriogenesis in a rabbit hindlimb ischemia model . Faseb J . 2003;17:100–102
  7. Roy S , Rothschild JG , Chen A . Vascular complications and gene therapy . Expert Opin Biol Ther . 2003;3:71–83
  8. Shyu KG , Chang H , Wang BW , Kuan P . Intramuscular vascular endothelial growth factor gene therapy in patients with chronic critical leg ischemia . Am J Med . 2003;114:85–92
  9. Waehre T , Damas JK , Gullestad L , Holm AM , Pedersen TR , Arnesen KE , et al.   Hydroxymethylglutaryl coenzyme a reductase inhibitors down-regulate chemokines and chemokine receptors in patients with coronary artery disease . J Am Coll Cardiol . 2003;41:1460–1467
  10. Garza L , Aude YW , Saucedo JF . Can we prevent in-stent restenosis? . Curr Opin Cardiol . 2002;17:518–525
  11. Klugherz BD , Song C , DeFelice S , Cui X , Lu Z , Connolly J , et al.   Gene delivery to pig coronary arteries from stents carrying antibody-tethered adenovirus . Hum Gene Ther . 2002;13:443–454
  12. Autieri MV , Carbone C , Mu A . Expression of allograft inflammatory factor-1 is a marker of activated human vascular smooth muscle cells and arterial injury . Arterioscler Thromb Vasc Biol . 2000;20:1737–1744
  13. Lee M , Rentz J , Han SO , Bull DA , Kim SW . Water-soluble lipopolymer as an efficient carrier for gene delivery to myocardium . Gene Ther . 2003;10:585–593
  14. Hamawy AH , Lee LY , Crystal RG , Rosengart TK . Cardiac angiogenesis and gene therapy: a strategy for myocardial revascularization . Curr Opin Cardiol . 1999;14:515–522
  15. Davis HL , Whalen RG , Demeneix BA . Direct gene transfer into skeletal muscle in vivo: factors affecting efficiency of transfer and stability of expression . Hum Gene Ther . 1993;4:151–159
  16. Kay MA , Liu D , Hoogerbrugge PM . Gene therapy . Proc Natl Acad Sci USA . 1997;94:12744–12746
  17. Niven R , Zhang Y , Smith J . Toward development of a non-viral gene therapeutic . Adv Drug Deliv Rev . 1997;26:135–150
  18. Mountain A . Gene therapy: the first decade . Trends Biotechnol . 2000;18:119–128
  19. Lehrman S . Virus treatment questioned after gene therapy death . Nature . 1999;401:517–518
  20. Ledley FD . Non-viral gene therapy . Curr Opin Biotechnol . 1994;5:626–636
  21. Mir LM , Bureau MF , Gehl J , Rangara R , Rouy D , Caillaud JM , et al.   High-efficiency gene transfer into skeletal muscle mediated by electric pulses . Proc Natl Acad Sci USA . 1999;96:4262–4267
  22. Rizzuto G , Cappelletti M , Maione D , Savino R , Lazzaro D , Costa P , et al.   Efficient and regulated erythropoietin production by naked DNA injection and muscle electroporation . Proc Natl Acad Sci USA . 1999;96:6417–6422
  23. Scherman D , Bigey P , Bureau MF . Applications of plasmid electrotransfer . Technol Cancer Res Treat . 2002;1:351–354
  24. Fattori E , La Monica N , Ciliberto G , Toniatti C . Electrogene-transfer: a new approach for muscle gene delivery . Somat Cell Mol Genet . 2002;27:75–83
  25. Felgner PL , Gadek TR , Holm M , Roman R , Chan HW , Wenz M , et al.   Lipofection: a highly efficient, lipidmediated DNA-transfection procedure . Proc Natl Acad Sci USA . 1987;84:7413–7417
  26. Lleres D , Dauty E , Behr JP , Mely Y , Duportail G . DNA condensation by an oxidizable cationic detergent. Interactions with lipid vesicles . Chem Phys Lipids . 2001;111:59–71
  27. Dauty E , Remy JS , Blessing T , Behr JP . Dimerizable cationic detergents with a low cmc condense plasmid DNA into nanometric particles and transfect cells in culture . J Am Chem Soc . 2001;123:9227–9234
  28. Zabner J , Fasbender AJ , Moninger T , Poellinger KA , Welsh MJ . Cellular and molecular barriers to gene transfer by a cationic lipid . J Biol Chem . 1995;270:18997–19007
  29. Felgner JH , Kumar R , Sridhar CN , Wheeler CJ , Tsai YJ , Border R , et al.   Enhanced gene delivery and mechanism studies with a novel series of cationic lipid formulations . J Biol Chem . 1994;269:2550–2561
  30. Legendre JY , Szoka FC . Delivery of plasmid DNA into mammalian cell lines using pH-sensitive liposomes: comparison with cationic liposomes . Pharm Res . 1992;9:1235–1242
  31. Turunen MP , Hiltunen MO , Ruponen M , Virkamaki L , Szoka FC , Urtti A , et al.   Efficient adventitial gene delivery to rabbit carotid artery with cationic polymer-plasmid complexes . Gene Ther . 1999;6:6–11
  32. Horiguchi Y , Larchian WA , Kaplinsky R , Fair WR , Heston WD . Intravesical liposome-mediated interleukin-2 gene therapy in orthotopic murine bladder cancer model . Gene Ther . 2000;7:844–851
  33. Domashenko A , Gupta S , Cotsarelis G . Efficient delivery of transgenes to human hair follicle progenitor cells using topical lipoplex . Nat Biotechnol . 2000;18:420–423
  34. Kwoh DY , Coffin CC , Lollo CP , Jovenal J , Banaszczyk MG , Mullen P , et al.   Stabilization of poly-L-lysine/DNA polyplexes for in vivo gene delivery to the liver . Biochim Biophys Acta . 1999;1444:171–190
  35. Richardson SC , Kolbe HV , Duncan R . Potential of low molecular mass chitosan as a DNA delivery system: biocompatibility, body distribution and ability to complex and protect DNA . Int J Pharm . 1999;178:231–243
  36. Gonsho A , Irie K , Susaki H , Iwasawa H , Okuno S , Sugawara T . Tissue-targeting ability of saccharide-poly (L-lysine) conjugates . Biol Pharm Bull . 1994;17:275–282
  37. Liu G , Molas M , Grossmann GA , Pasumarthy M , Perales JC , Cooper MJ , et al.   Biological properties of poly-L-lysine-DNA complexes generated by cooperative binding of the polycation . J Biol Chem . 2001;276:34379–34387
  38. Hansma HG , Golan R , Hsieh W , Lollo CP , Mullen-Ley P , Kwoh D . DNA condensation for gene therapy as monitored by atomic force microscopy . Nucleic Acids Res . 1998;26:2481–2487
  39. Gao X , Huang L . Potentiation of cationic liposomemediated gene delivery by polycations . Biochemistry . 1996;35:1027–1036
  40. Baeza I , Gariglio P , Rangel LM , Chavez P , Cervantes L , Arguello C , et al.   Electron microscopy and biochemical properties of polyamine-compacted DNA . Biochemistry . 1987;26:6387–6392
  41. 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 . 1994;5:1095–1104
  42. Wagner E , Plank C , Zatloukal K , Cotten M , Birnstiel ML . Influenza virus hemagglutinin HA-2N-terminal fusogenic peptides augment gene transfer by transferrinpolylysine-DNA complexes: toward a synthetic virus-like gene-transfer vehicle . Proc Natl Acad Sci USA . 1992;89:7934–7938
  43. 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 . 1998;5:1235–1243
  44. Wagner E , Cotten M , Foisner R , Birnstiel ML . Transferrinpolycation-DNA complexes: the effect of polycations on the structure of the complex and DNA delivery to cells . Proc Natl Acad Sci USA . 1991;88:4255–4259
  45. Ferkol T , Pellicena-Palle A , Eckman E , Perales JC , Trzaska T , Tosi M , et al.   Immunologic responses to gene transfer into mice via the polymeric immunoglobulin receptor . Gene Ther . 1996;3:669–678
  46. Godbey WT , Wu KK , Mikos AG . Poly(ethylenimine) and its role in gene delivery . J Control Release . 1999;60:149–160
  47. Dunlap DD , Maggi A , Soria MR , Monaco L . Nanoscopic structure of DNA condensed for gene delivery . Nucleic Acids Res . 1997;25:3095–3101
  48. Boussif O , Lezoualc'h F , Zanta MA , Mergny MD , Scherman D , Demeneix B , et al.   A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine . Proc Natl Acad Sci USA . 1995;92:7297–7301
  49. Godbey WT , Barry MA , Saggau P , Wu KK , Mikos AG . Poly(ethylenimine)-mediated transfection: a new paradigm for gene delivery . J Biomed Mater Res . 2000;51:321–328
  50. Ferrari S , Moro E , Pettenazzo A , Behr JP , Zacchello F , Scarpa M . ExGen 500 is an efficient vector for gene delivery to lung epithelial cells in vitro and in vivo . Gene Ther . 1997;4:1100–1106
  51. Fischer D , Bieber T , Li Y , Elsasser HP , Kissel T . A novel non-viral vector for DNA delivery based on low molecular weight, branched polyethylenimine: effect of molecular weight on transfection efficiency and cytotoxicity . Pharm Res . 1999;16:1273–1279
  52. Jeong JH , Song SH , Lim DW , Lee H , Park TG . DNA transfection using linear poly(ethylenimine) prepared by controlled acid hydrolysis of poly(2-ethyl-2-oxazoline) . J Control Release . 2001;73:391–399
  53. Ogris M , Brunner S , Schuller S , Kircheis R , Wagner E . PEGylated DNA/transferrin-PEI complexes: reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery . Gene Ther . 1999;6:595–605
  54. Yang NS , Burkholder J , Roberts B , Martinell B , McCabe D . In vivo and in vitro gene transfer to mammalian somatic cells by particle bombardment . Proc Natl Acad Sci USA . 1990;87:9568–9572
  55. Condon C , Watkins SC , Celluzzi CM , Thompson K , Falo LD . DNA-based immunization by in vivo transfection of dendritic cells . Nat Med . 1996;2:1122–1128
  56. Sawamura D , Ina S , Itai K , Meng X , Kon A , Tamai K , et al.   In vivo gene introduction into keratinocytes using jet injection . Gene Ther . 1999;6:1785–1787
  57. Neumann E , Schaefer-Ridder M , Wang Y , Hofschneider PH . Gene transfer into mouse lyoma cells by electroporation in high electric fields . Embo J . 1982;1:841–845
  58. Mathiesen I . Electropermeabilization of skeletal muscle enhances gene transfer in vivo . Gene Ther . 1999;6:508–514
  59. Yu T , Wang Z , Mason TJ . A review of research into the uses of low level ultrasound in cancer therapy . Ultrason Sonochem . 2004;11:95–103
  60. Apfel RE . Acoustic cavitation: a possible consequence of biomedical uses of ultrasound . Br J Cancer Suppl . 1982;45:140–146
  61. Nyborg WL . Ultrasonic microstreaming and related phenomena . Br J Cancer Suppl . 1982;5:156–160
  62. Church CC , Carstensen EL . “Stable” inertial cavitation . Ultrasound Med Biol . 2001;27:1435–1437
  63. Miller MW , Miller DL , Brayman AA . A review of in vitro bioeffects of inertial ultrasonic cavitation from a mechanistic perspective . Ultrasound Med Biol . 1996;22:1131–1154
  64. Apfel RE , Holland CK . Gauging the likelihood of cavitation from short-pulse, low-duty cycle diagnostic ultrasound . Ultrasound Med Biol . 1991;17:179–185
  65. Meltzer RS . Food and Drug Administration ultrasound device regulation: the output display standard, the “mechanical index,” and ultrasound safety . J Am Soc Echocardiogr . 1996;9:216–220
  66. McNeil PL . Incorporation of macromolecules into living cells . Methods Cell Biol . 1989;29:153–173
  67. Tachibana K , Uchida T , Ogawa K , Yamashita N , Tamura K . Induction of cell-membrane porosity by ultrasound . Lancet . 1999;353:1409
  68. Taniyama Y , Tachibana K , Hiraoka K , Aoki M , Yamamoto S , Matsumoto K , et al.   Development of safe and efficient novel nonviral gene transfer using ultrasound: enhancement of transfection efficiency of naked plasmid DNA in skeletal muscle . Gene Ther . 2002;9:372–380
  69. Taniyama Y , Tachibana K , Hiraoka K , Namba T , Yamasaki K , Hashiya N , et al.   Local delivery of plasmid DNA into rat carotid artery using ultrasound . Circulation . 2002;105:1233–1239
  70. Fechheimer M , Boylan JF , Parker S , Sisken JE , Patel GL , Zimmer SG . Transfection of mammalian cells with plasmid DNA by scrape loading and sonication loading . Proc Natl Acad Sci USA . 1987;84:8463–8467
  71. Kim HJ , Greenleaf JF , Kinnick RR , Bronk JT , Bolander ME . Ultrasound-mediated transfection of mammalian cells . Hum Gene Ther . 1996;7:1339–1346
  72. Lawrie A , Brisken AF , Francis SE , Tayler DI , Chamberlain J , Crossman DC , et al.   Ultrasound enhances reporter gene expression after transfection of vascular cells in vitro . Circulation . 1999;99:2617–2620
  73. Feril LB , Ogawa R , Kobayashi H , Kikuchi H , Kondo T . Ultrasound enhances liposome-mediated gene transfection . Ultrason Sonochem . 2005;12:489–493
  74. Deshpande MC , Prausnitz MR . Synergistic effect of ultrasound and PEI on DNA transfection in vitro . J Control Release . 2007;118:126–135
  75. Chen WS , Matula TJ , Crum LA . The disappearance of ultrasound contrast bubbles: observations of bubble dissolution and cavitation nucleation . Ultrasound Med Biol . 2002;28:793–803
  76. Allen JS , May DJ , Ferrara KW . Dynamics of therapeutic ultrasound contrast agents . Ultrasound Med Biol . 2002;28:805–816
  77. Feril LB , Kondo T , Zhao QL , Ogawa R , Tachibana K , Kudo N , et al.   Enhancement of ultrasound-induced apoptosis and cell lysis by echo-contrast agents . Ultrasound Med Biol . 2003;29:331–337
  78. Vannan M , McCreery T , Li P , Han Z , Unger E , Kuersten B , et al.   Ultrasound-mediated transfection of canine myocardium by intravenous administration of cationic microbubble-linked plasmid DNA . J Am Soc Echocardiogr . 2002;15:214–218
  79. Alter A , Rozenszajn LA , Miller HI , Rosenschein U . Ultrasound inhibits the adhesion and migration of smooth muscle cells in vitro . Ultrasound Med Biol . 1998;24:711–721
  80. Boucaud A , Garrigue MA , Machet L , Vaillant L , Patat F . Effect of sonication parameters on transdermal delivery of insulin to hairless rats . J Control Release . 2002;81:113–119
  81. Kost J . Ultrasound-assisted insulin delivery and noninvasive glucose sensing . Diabetes Technol Ther . 2002;4:489–497
  82. Smith NB , Lee S , Shung KK . Ultrasound-mediated transdermal in vivo transport of insulin with low-profile cymbal arrays . Ultrasound Med Biol . 2003;29:1205–1210
  83. Merino G , Kalia YN , Delgado-Charro MB , Potts RO , Guy RH . Frequency and thermal effects on the enhancement of transdermal transport by sonophoresis . J Control Release . 2003;88:85–94
  84. Mitragotri S , Kost J . Low-frequency sonophoresis: a noninvasive method of drug delivery and diagnostics . Biotechnol Prog . 2000;16:488–492
  85. Mitragotri S , Kost J . Transdermal delivery of heparin and low-molecular weight heparin using low-frequency ultrasound . Pharm Res . 2001;18:1151–1156
  86. Yamashita T , Sonoda S , Suzuki R , Arimura N , Tachibana K , Maruyama K , et al.   A novel bubble liposome and ultrasound-mediated gene transfer to ocular surface: RC-1 cells in vitro and conjunctiva in vivo . Exp Eye Res . 2007;85:741–748
  87. Shen ZP, Brayman AA, Chen L, Miao CH. Ultrasound with microbubbles enhances gene expression of plasmid DNA in the liver via intraportal delivery. Gene Ther 2008 (In press).
  88. Sheyn D , Kimelman-Bleich N , Pelled G , Zilberman Y , Gazit D , Gazit Z . Ultrasound-based nonviral gene delivery induces bone formation in vivo . Gene Ther . 2008;15:257–266
  89. Chumakova OV , Liopo AV , Andreev VG , Cicenaite I , Evers BM , Chakrabarty S , et al.   Composition of PLGA and PEI/DNA nanoparticles improves ultrasound-mediated gene delivery in solid tumors in vivo . Cancer Lett . 2008;261:215–225
  90. Inagaki H , Suzuki J , Ogawa M , Taniyama Y , Morishita R , Isobe M . Ultrasound-microbubble-mediated NF-kappaB decoy transfection attenuates neointimal formation after arterial injury in mice . J Vasc Res . 2006;43:12–18
  91. Korpanty G , Chen S , Shohet RV , Ding J , Yang B , Frenkel PA , et al.   Targeting of VEGF-mediated angiogenesis to rat myocardium using ultrasonic destruction of microbubbles . Gene Ther . 2005;12:1305–1312
  92. Bekeredjian R , Chen S , Grayburn PA , Shohet RV . Augmentation of cardiac protein delivery using ultrasound targeted microbubble destruction . Ultrasound Med Biol . 2005;31:687–691
  93. Hashiya N , Aoki M , Tachibana K , Taniyama Y , Yamasaki K , Hiraoka K , et al.   Local delivery of E2F decoy oligodeoxynucleotides using ultrasound with microbubble agent (Optison) inhibits intimal hyperplasia after balloon injury in rat carotid artery model . Biochem Biophys Res Commun . 2004;317:508–514
  94. Shimamura M , Sato N , Taniyama Y , Yamamoto S , Endoh M , Kurinami H , et al.   Development of efficient plasmid DNA transfer into adult rat central nervous system using microbubble-enhanced ultrasound . Gene Ther . 2004;11:1532–1539
  95. Azuma H , Tomita N , Kaneda Y , Koike H , Ogihara T , Katsuoka Y , et al.   Transfection of NFκB-decoy oligo-deoxynucleotides using efficient ultrasound-mediated gene transfer into donor kidneys prolonged survival of rat renal allografts . Gene Ther . 2003;10:415–425
  96. Akowuah EF , Gray C , Lawrie A , Sheridan PJ , Su CH , Bettinger T , et al.   Ultrasound-mediated delivery of TIMP-3 plasmid DNA into saphenous vein leads to increased lumen size in a porcine interposition graft model . Gene Ther . 2005;12:1154–1157
  97. Miller DL , Bao S , Gies RA , Thrall BD . Ultrasonic enhancement of gene transfection in murine melanoma tumors . Ultrasound Med Biol . 1999;25:1425–1430
  98. Christiansen JP , French BA , Klibanov AL , Kaul S , Lindner JR . Targeted tissue transfection with ultrasound destruction of plasmid-bearing cationic microbubbles . Ultrasound Med Biol . 2003;29:1759–1767
  99. Huber PE , Pfisterer P . In vitro and in vivo transfection of plasmid DNA in the Dunning prostate tumor R3327-AT1 is enhanced by focused ultrasound . Gene Ther . 2000;7:1516–1525
  100. Amabile PG , Waugh JM , Lewis TN , Elkins CJ , Janas W , Dake MD . High-efficiency endovascular gene delivery via therapeutic ultrasound . J Am Coll Cardiol . 2001;37:1975–1980
  101. Manome Y , Nakamura M , Ohno T , Furuhata H . Ultrasound facilitates transduction of naked plasmid DNA into colon carcinoma cells in vitro and in vivo . Hum Gene Ther . 2000;11:1521–1528
  102. Lu QL , Liang HD , Partridge T , Blomley MJ . Microbubble ultrasound improves the efficiency of gene transduction in skeletal muscle in vivo with reduced tissue damage . Gene Ther . 2003;10:396–405
  103. Teupe C , Richter S , Fisslthaler B , Randriamboavonjy V , Ihling C , Fleming I , et al.   Vascular gene transfer of phosphomimetic endothelial nitric oxide synthase (S1177D) using ultrasound-enhanced destruction of plasmid-loaded microbubbles improves vasoreactivity . Circulation . 2002;105:1104–1109
  104. Shohet RV , Chen S , Zhou YT , Wang Z , Meidell RS , Unger RH , et al.   Echocardiographic destruction of albumin microbubbles directs gene delivery to the myocardium . Circulation . 2000;101:2554–2556
  105. Newman CM , Bettinger T . Gene therapy progress and prospects: ultrasound for gene transfer . Gene Ther . 2007;14:465–475
  106. Villanueva FS , Jankowski RJ , Klibanov S , Pina ML , Alber SM , Watkins SC , et al.   Microbubbles targeted to intercellular adhesion molecule-1 bind to activated coronary artery endothelial cells . Circulation . 1998;98:1–5
  107. Lanza GM , Wallace KD , Scott MJ , Cacheris WP , Abendschein DR , Christy DH , et al.   A novel site-targeted ultrasonic contrast agent with broad biomedical application . Circulation . 1996;94:3334–3340
  108. Klibanov AL . Targeted delivery of gas-filled microspheres, contrast agents for ultrasound imaging . Adv Drug Deliv Rev . 1999;37:139–157
  109. Bian AN , Gao YH , Tan KB , Liu P , Zeng GJ , Zhang X , et al.   Preparation of human hepatocellular carcinomatargeted liposome microbubbles and their immunological properties . World J Gastroenterol . 2004;10:3424–3427

PII: S1873-9598(08)70009-7

doi: 10.1016/S1873-9598(08)70009-7

International Journal of Gerontology
Volume 2, Issue 2 , Pages 35-47 , June 2008