Nonviral Technologies for Gene Therapy in Cardiovascular Research
Article Outline
Summary
Gene therapy, which is still at an experimental stage, is a technique that attempts to correct or prevent a disease by delivering genes into an individual's cells and tissues. In gene delivery, a vector is a vehicle for transferring genetic material into cells and tissues. Synthetic vectors are considered to be prerequisites for gene delivery, because viral vectors have fundamental problems in relation to safety issues as well as large-scale production. Among the physical approaches, ultrasound with its associated bioeffects such as acoustic cavitation, especially inertial cavitation, can increase the permeability of cell membranes to macromolecules such as plasmid DNA. Microbubbles or ultrasound contrast agents lower the threshold for cavitation by ultrasound energy. Furthermore, ultrasound-enhanced gene delivery using polymers or other nonviral vectors may hold much promise for the future but is currently at the preclinical stage. We all know aging is cruel and inevitable. Currently, among the promising areas for gene therapy in acquired diseases, the incidences of cancer and ischemic cardiovascular diseases are strongly correlated with the aging process. As a result, gene therapy technology may play important roles in these diseases in the future. This brief review focuses on understanding the barriers to gene transfer as well as describing the useful nonviral vectors or tools that are applied to gene delivery and introducing feasible models in terms of ultrasound-based gene delivery.
Key Words: cavitation , gene therapy , microbubble , transfection efficiency , ultrasound , vector
No full text is available. To read the body of this article, please view the PDF online.
References
- . Science, medicine, and the future. Gene therapy . BMJ . 1997;315:1289–1292
- . Recombinant gene expression in vivo within endothelial cells of the arterial wall . Science . 1989;244:1342–1344
- T lymphocyte-directed gene therapy for ADA-SCID: initial trial results after 4 years . Science . 1995;270:475–480
- The Journal of Gene Medicine Clinical Trial Web site . http://www.wiley.co.uk/genetherapy/clinical/ Updated: March 2008. [Accessed: April 2008]
- Regional Angiogenesis with Vascular Endothelial Growth Factor (VEGF) in peripheral arterial disease: design of the RAVE trial . Am Heart J . 2003;145:1114–1118
- Fibroblast growth factor 4 induces vascular permeability, angiogenesis and arteriogenesis in a rabbit hindlimb ischemia model . Faseb J . 2003;17:100–102
- . Vascular complications and gene therapy . Expert Opin Biol Ther . 2003;3:71–83
- . Intramuscular vascular endothelial growth factor gene therapy in patients with chronic critical leg ischemia . Am J Med . 2003;114:85–92
- 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
- . Can we prevent in-stent restenosis? . Curr Opin Cardiol . 2002;17:518–525
- Gene delivery to pig coronary arteries from stents carrying antibody-tethered adenovirus . Hum Gene Ther . 2002;13:443–454
- . 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
- . Water-soluble lipopolymer as an efficient carrier for gene delivery to myocardium . Gene Ther . 2003;10:585–593
- . Cardiac angiogenesis and gene therapy: a strategy for myocardial revascularization . Curr Opin Cardiol . 1999;14:515–522
- . Direct gene transfer into skeletal muscle in vivo: factors affecting efficiency of transfer and stability of expression . Hum Gene Ther . 1993;4:151–159
- . Gene therapy . Proc Natl Acad Sci USA . 1997;94:12744–12746
- . Toward development of a non-viral gene therapeutic . Adv Drug Deliv Rev . 1997;26:135–150
- . Gene therapy: the first decade . Trends Biotechnol . 2000;18:119–128
- . Virus treatment questioned after gene therapy death . Nature . 1999;401:517–518
- . Non-viral gene therapy . Curr Opin Biotechnol . 1994;5:626–636
- High-efficiency gene transfer into skeletal muscle mediated by electric pulses . Proc Natl Acad Sci USA . 1999;96:4262–4267
- Efficient and regulated erythropoietin production by naked DNA injection and muscle electroporation . Proc Natl Acad Sci USA . 1999;96:6417–6422
- . Applications of plasmid electrotransfer . Technol Cancer Res Treat . 2002;1:351–354
- . Electrogene-transfer: a new approach for muscle gene delivery . Somat Cell Mol Genet . 2002;27:75–83
- Lipofection: a highly efficient, lipidmediated DNA-transfection procedure . Proc Natl Acad Sci USA . 1987;84:7413–7417
- . DNA condensation by an oxidizable cationic detergent. Interactions with lipid vesicles . Chem Phys Lipids . 2001;111:59–71
- . 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
- . Cellular and molecular barriers to gene transfer by a cationic lipid . J Biol Chem . 1995;270:18997–19007
- Enhanced gene delivery and mechanism studies with a novel series of cationic lipid formulations . J Biol Chem . 1994;269:2550–2561
- . Delivery of plasmid DNA into mammalian cell lines using pH-sensitive liposomes: comparison with cationic liposomes . Pharm Res . 1992;9:1235–1242
- Efficient adventitial gene delivery to rabbit carotid artery with cationic polymer-plasmid complexes . Gene Ther . 1999;6:6–11
- . Intravesical liposome-mediated interleukin-2 gene therapy in orthotopic murine bladder cancer model . Gene Ther . 2000;7:844–851
- . Efficient delivery of transgenes to human hair follicle progenitor cells using topical lipoplex . Nat Biotechnol . 2000;18:420–423
- Stabilization of poly-L-lysine/DNA polyplexes for in vivo gene delivery to the liver . Biochim Biophys Acta . 1999;1444:171–190
- . 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
- . Tissue-targeting ability of saccharide-poly (L-lysine) conjugates . Biol Pharm Bull . 1994;17:275–282
- Biological properties of poly-L-lysine-DNA complexes generated by cooperative binding of the polycation . J Biol Chem . 2001;276:34379–34387
- . DNA condensation for gene therapy as monitored by atomic force microscopy . Nucleic Acids Res . 1998;26:2481–2487
- . Potentiation of cationic liposomemediated gene delivery by polycations . Biochemistry . 1996;35:1027–1036
- Electron microscopy and biochemical properties of polyamine-compacted DNA . Biochemistry . 1987;26:6387–6392
- . 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
- . 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
- . The contribution of poly-L-lysine, epidermal growth factor and streptavidin to EGF/PLL/DNA polyplex formation . Gene Ther . 1998;5:1235–1243
- . 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
- Immunologic responses to gene transfer into mice via the polymeric immunoglobulin receptor . Gene Ther . 1996;3:669–678
- . Poly(ethylenimine) and its role in gene delivery . J Control Release . 1999;60:149–160
- . Nanoscopic structure of DNA condensed for gene delivery . Nucleic Acids Res . 1997;25:3095–3101
- 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
- . Poly(ethylenimine)-mediated transfection: a new paradigm for gene delivery . J Biomed Mater Res . 2000;51:321–328
- . ExGen 500 is an efficient vector for gene delivery to lung epithelial cells in vitro and in vivo . Gene Ther . 1997;4:1100–1106
- . 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
- . DNA transfection using linear poly(ethylenimine) prepared by controlled acid hydrolysis of poly(2-ethyl-2-oxazoline) . J Control Release . 2001;73:391–399
- . 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
- . In vivo and in vitro gene transfer to mammalian somatic cells by particle bombardment . Proc Natl Acad Sci USA . 1990;87:9568–9572
- . DNA-based immunization by in vivo transfection of dendritic cells . Nat Med . 1996;2:1122–1128
- In vivo gene introduction into keratinocytes using jet injection . Gene Ther . 1999;6:1785–1787
- . Gene transfer into mouse lyoma cells by electroporation in high electric fields . Embo J . 1982;1:841–845
- . Electropermeabilization of skeletal muscle enhances gene transfer in vivo . Gene Ther . 1999;6:508–514
- . A review of research into the uses of low level ultrasound in cancer therapy . Ultrason Sonochem . 2004;11:95–103
- . Acoustic cavitation: a possible consequence of biomedical uses of ultrasound . Br J Cancer Suppl . 1982;45:140–146
- . Ultrasonic microstreaming and related phenomena . Br J Cancer Suppl . 1982;5:156–160
- . “Stable” inertial cavitation . Ultrasound Med Biol . 2001;27:1435–1437
- . A review of in vitro bioeffects of inertial ultrasonic cavitation from a mechanistic perspective . Ultrasound Med Biol . 1996;22:1131–1154
- . Gauging the likelihood of cavitation from short-pulse, low-duty cycle diagnostic ultrasound . Ultrasound Med Biol . 1991;17:179–185
- . 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
- . Incorporation of macromolecules into living cells . Methods Cell Biol . 1989;29:153–173
- . Induction of cell-membrane porosity by ultrasound . Lancet . 1999;353:1409
- 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
- Local delivery of plasmid DNA into rat carotid artery using ultrasound . Circulation . 2002;105:1233–1239
- . Transfection of mammalian cells with plasmid DNA by scrape loading and sonication loading . Proc Natl Acad Sci USA . 1987;84:8463–8467
- . Ultrasound-mediated transfection of mammalian cells . Hum Gene Ther . 1996;7:1339–1346
- Ultrasound enhances reporter gene expression after transfection of vascular cells in vitro . Circulation . 1999;99:2617–2620
- . Ultrasound enhances liposome-mediated gene transfection . Ultrason Sonochem . 2005;12:489–493
- . Synergistic effect of ultrasound and PEI on DNA transfection in vitro . J Control Release . 2007;118:126–135
- . The disappearance of ultrasound contrast bubbles: observations of bubble dissolution and cavitation nucleation . Ultrasound Med Biol . 2002;28:793–803
- . Dynamics of therapeutic ultrasound contrast agents . Ultrasound Med Biol . 2002;28:805–816
- Enhancement of ultrasound-induced apoptosis and cell lysis by echo-contrast agents . Ultrasound Med Biol . 2003;29:331–337
- Ultrasound-mediated transfection of canine myocardium by intravenous administration of cationic microbubble-linked plasmid DNA . J Am Soc Echocardiogr . 2002;15:214–218
- . Ultrasound inhibits the adhesion and migration of smooth muscle cells in vitro . Ultrasound Med Biol . 1998;24:711–721
- . Effect of sonication parameters on transdermal delivery of insulin to hairless rats . J Control Release . 2002;81:113–119
- . Ultrasound-assisted insulin delivery and noninvasive glucose sensing . Diabetes Technol Ther . 2002;4:489–497
- . Ultrasound-mediated transdermal in vivo transport of insulin with low-profile cymbal arrays . Ultrasound Med Biol . 2003;29:1205–1210
- . Frequency and thermal effects on the enhancement of transdermal transport by sonophoresis . J Control Release . 2003;88:85–94
- . Low-frequency sonophoresis: a noninvasive method of drug delivery and diagnostics . Biotechnol Prog . 2000;16:488–492
- . Transdermal delivery of heparin and low-molecular weight heparin using low-frequency ultrasound . Pharm Res . 2001;18:1151–1156
- 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
- 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).
- . Ultrasound-based nonviral gene delivery induces bone formation in vivo . Gene Ther . 2008;15:257–266
- Composition of PLGA and PEI/DNA nanoparticles improves ultrasound-mediated gene delivery in solid tumors in vivo . Cancer Lett . 2008;261:215–225
- . Ultrasound-microbubble-mediated NF-kappaB decoy transfection attenuates neointimal formation after arterial injury in mice . J Vasc Res . 2006;43:12–18
- Targeting of VEGF-mediated angiogenesis to rat myocardium using ultrasonic destruction of microbubbles . Gene Ther . 2005;12:1305–1312
- . Augmentation of cardiac protein delivery using ultrasound targeted microbubble destruction . Ultrasound Med Biol . 2005;31:687–691
- 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
- Development of efficient plasmid DNA transfer into adult rat central nervous system using microbubble-enhanced ultrasound . Gene Ther . 2004;11:1532–1539
- 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
- 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
- . Ultrasonic enhancement of gene transfection in murine melanoma tumors . Ultrasound Med Biol . 1999;25:1425–1430
- . Targeted tissue transfection with ultrasound destruction of plasmid-bearing cationic microbubbles . Ultrasound Med Biol . 2003;29:1759–1767
- . 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
- . High-efficiency endovascular gene delivery via therapeutic ultrasound . J Am Coll Cardiol . 2001;37:1975–1980
- . Ultrasound facilitates transduction of naked plasmid DNA into colon carcinoma cells in vitro and in vivo . Hum Gene Ther . 2000;11:1521–1528
- . Microbubble ultrasound improves the efficiency of gene transduction in skeletal muscle in vivo with reduced tissue damage . Gene Ther . 2003;10:396–405
- 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
- Echocardiographic destruction of albumin microbubbles directs gene delivery to the myocardium . Circulation . 2000;101:2554–2556
- . Gene therapy progress and prospects: ultrasound for gene transfer . Gene Ther . 2007;14:465–475
- Microbubbles targeted to intercellular adhesion molecule-1 bind to activated coronary artery endothelial cells . Circulation . 1998;98:1–5
- A novel site-targeted ultrasonic contrast agent with broad biomedical application . Circulation . 1996;94:3334–3340
- . Targeted delivery of gas-filled microspheres, contrast agents for ultrasound imaging . Adv Drug Deliv Rev . 1999;37:139–157
- 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
© 2008 Elsevier B.V. All rights reserved.
