Abstract
Gene therapy can be defined as the introduction of genetic material into a particular cell or tissue type to alter the pattern of gene expression to produce a therapeutic effect. There are three critical components to consider in designing and optimizing a gene therapy strategy for the treatment of any disease: a vector to introduce the gene, a device and procedure for delivering the vector to the appropriate tissue or organ, and a therapeutic gene. Each component must be chosen or modified to best suit the specific characteristics of the particular disease of interest.
The comments and opinions in this paper reflect those of the author as an individual and do not necessarily represent the views of the U.S. National Institutes of Health, the Department of Health and Human Services, or the U.S. Government.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Baumgartner I, Pieczek A, Manor O, Blair R, Kearney M, Walsh K, Isner JM (1998) Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. Circulation 97: 1114–1123
Baumgartner I, Rauh G, Pieczek A, Wuensch D, Magner M, Kearney M, Schainfeld R, Isner JM (2000) Lower-extremity edema associated with gene transfer of naked DNA encoding vascular endothelial growth factor. Ann Intern Med 132: 880–884
Boehm M, Yoshimoto T, Crook MF, Nallamshetty S, True A, Nabel GJ, Nabel EG (2002) A growth factor-dependent nuclear kinase phosphorylates p27(Kipl) and regulates cell cycle progression. EMBO J 21: 3390–3401
Boris L, Temin H: Recent advances in retrovirus vector technology (1993) Curr Opin Genet Dev 3:102–109
Buchschacher GL Jr, Wong-Staal F (2000) Development of lentiviral vectors for gene therapy for human diseases. Blood 95: 2499–2504
Burns JC, Friedmann T, Driever W, Burrascano M, Yee JK (1993) Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: concentration to very high titer and efficient gene transfer into mammalian and non-mammalian cells. Proc Natl Acad Sci USA 90: 8033–8037
Carmeliet P, Jain RK (2000) Angiogenesis in cancer and other diseases. Nature 407: 249–257
Coburn GA, Cullen BR (2002) Potent and specific inhibition of human immunodeficiency virus type 1 replication by RNA interference. J Virol 76: 9225–9231
DeMatteo RP, Markmann JF, Kozarsky KF, Barker CF, Raper SE (1996) Prolongation of adenoviral transgene expression in mouse liver by T lymphocyte subset depletion. Gene Ther 3: 4–12
Feigner PL, Gadek TR, Holm M, Roman R, Chan HW, Wenz M, Northrop JP, Ringold GM, Danielsen M (1987) Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Nail Acad Sci U S A 84: 7413–7417
Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391: 806–811
Folkman J (1971) Tumor angiogenesis: Therapeutic implications. N Engl J Med 285: 1182–1186
Friedmann T (1992) A brief history of gene therapy. Nat Genet 2: 93–98
Giordano FJ, Ping P, McKirnan MD, Nozaki S, DeMaria AN, Dillmann WH, Mathieu-Costello O, Hammond HK (1996) Intracoronary gene transfer of fibroblast growth factor-5 increases blood flow and contractile function in an ischemic region of the heart. Nat Med 2: 534–539
Grishok A, Tabara H, Mello CC (2000) Genetic requirements for inheritance of RNAi in C. elegans. Science 287: 2494–2497
Gurwith MJ, Horwith GS, Impellizzeri CA, Davis AR, Lubeck MD, Hung PP (1989) Current use and future directions of adenovirus vaccine. Semin Resp Inf 4: 299–303
Harada K, Grossman W, Friedman M, Edelman ER, Prasad PV, Keighley CS, Manning WJ, Sellke FW, Simons M (1994) Basic fibroblast growth factor improves myocardial function in chronically ischemic porcine hearts. J Clin Invest 94: 623–630
Heldman AW, Cheng L, Jenkins GM, Heller PF, Kim DW, Ware M Jr, Nater C, Hruban RH, Rezai B, Abella BS, Bunge KE, Kinsella JL, Sollott SJ, Lakatta EG, Brinker JA, Hunter WL, Froehlich JP (2001) Paclitaxel stent coating inhibits neointimal hyperplasia at 4 weeks in a porcine model of coronary restenosis. Circulation 103: 2289–2295
Horwitz M (1990) The adenoviruses. In: Fields B, Knipe D (eds): Virology. Raven Press, New York, pp 1723–1742
Isner JM, Pieczek A, Schainfeld R, Blair R, Haley L, Asahara T, Rosenfield K, Razvi S, Walsh K, Symes JF (1996) Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb. Lancet 348: 370–374
Jacque JM, Triques K, Stevenson M (2002) Modulation of HIV-1 replication by RNA interference. Nature 418: 435–438
Kolodziejczyk SM, Wang L, Balazsi K, DeRepentigny Y, Kothary R, Megeney LA (1999) MEF2 is upregulated during cardiac hypertrophy and is required for normal post-natal growth of the myocardium. Curr Biol 9: 1203–6
Kotani H, Newton PB 3rd, Zhang S, Chiang YL, Otto E, Weaver L, Blaese RIVI, Anderson WF, McGarrity GJ (1994) Improved methods of retroviral vector transduction and production for gene therapy. Hum Gene Ther 5: 19–28
Kremer EJ, Perricaudet M (1995) Adenovirus and adeno-associated virus mediated gene transfer. Br Med Bull 51: 31–44
Lasic DD, Papahadjopoulos D (1995) Liposomes revisited. Science 267; 1275–1276
Lin H, Parmacek MS, Morle G (1990) Expression of recombinant genes in myocardium in vivo after direct injection of DNA. Circulation 82: 2217–2221
Lin Q, Lu J,Yanagisawa H,Webb R, Lyons GE, Richardson JA, Olson EN (1998) Requirement of the MADS-box transcription factor MEF2C for vascular development. Development 125: 4565–74
Losordo DW, Vale PR, Symes JF, Dunnington CH, Esakof DD, Maysky M, Ashare AB, Lathi K, Isner JM (1998) Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia. Circulation 98: 2800–2804
Lu J, McKinsey TA, Nicol RL, Olson EN (2000) Signal-dependent activation of the MEF2 transcription factor by dissociation from histone deacetylases. Proc Natl Acad Sci U S A 97: 4070–5
Mann MJ, Whittemore AD, Donaldson MC, Belkin M, Conte MS, Polak JF, Orav EJ, Ehsan A, Dell’Acqua G, Dzau VJ (1999) Ex-vivo gene therapy of human vascular bypass grafts with E2F decoy: the PREVENT single-centre, randomised, controlled trial. Lancet 354: 1493–1498
McManus MT, Sharp PA (2002) Gene silencing in mammals by small interfering RNAs. Nat Rev Genet 3: 737–747
Miller A (1992) Retroviral vectors. Curr Top Microbiol Immunol 158: 1–24
Miller D, Adam M, Miller A (1990) Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol Cell Biol 10: 4239–4242
Nabel EG, Plautz G, Nabel GJ (1990) Site-specific gene expression in vivo by direct gene transfer into the arterial wall. Science 249: 1285–1288
Nabel E, Plautz G, Nabel G (1992) Transduction of a foreign histocompatibility gene into the arterial wall induces vasculitis. Proc Natl Acad Sci USA 89: 5157–5161
Nahreini P, Larsen S, Srivastava A (1992) Cloning and integration of DNA fragments in human cells via the inverted terminal repeats of the adeno-associated virus 2 genome. Gene 119: 265–272
Naldini L, Blomer U, Gallay P, Ory D, Mulligan R, Gage FH, Verma IM, Trono D (1996) In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272: 263–267
Novina CD, Murray MF, Dykxhoorn DM, Beresford PJ, Riess J, Lee SK, Coll-man RG, Lieberman J, Shankar P, Sharp PA (2002) siRNA-directed inhibition of HIV-1 infection. Nat Med 8: 681–686
Otto E, Jones-Trower A, Vanin EF, Stambaugh K, Mueller SN, Anderson WF, McGarrity GJ (1994) Characterization of a replication-competent retrovirus resulting from recombination of packaging and vector sequences. Hum Gene Ther 5: 567–575
Passier R, Zeng H, Frey N, Naya FJ, Nicol RL, McKinsey TA, Overbeek P, Richardson JA, Grant SR, Olson EN (2000) CaM kinase signaling induces cardiac hypertrophy and activates the MEF2 transcription factor in vivo. J Clin Invest 105: 1395–406
Pu LQ, Sniderman AD, Brassard R, Lachapelle KJ, Graham AM, Lisbona R, Symes JF (1993) Enhanced revascularization of the ischemic limb by angiogenic therapy. Circulation 88: 208–215
Rajagopalan S, Shah M, Luciano A, Crystal R, Nabel EG (2001) Adenovirusmediated gene transfer of VEGF(121) improves lower-extremity endothelial function and flow reserve. Circulation 104: 753–755
Ranga U, Woffendin C, Verma S, Xu L, June CH, Bishop DK, Nabel GJ (1998) Enhanced T cell engraftment after retroviral delivery of an antiviral gene in HIV-infected individuals. Proc Natl Acad Sci U S A 95: 1201–1206
Roe T, Reynolds T, Uy G, Brown P (1993) Integration of murine leukemia virus DNA depends on mitosis. EMBO J 12: 2099–2108
Rolling F, Samulski RJ (1995) AAV as a viral vector for human gene therapy. Generation of recombinant virus. Mol Biotechnol 3: 9–15
Rosengart TK, Lee LY, Patel SR, Kligfield PD, Okin PM, Hackett NR, Isom OW, Crystal RG (1999) Six-month assessment of a phase I trial of angiogenic gene therapy for the treatment of coronary artery disease using direct intramyocardial administration of an adenovirus vector expressing the VEGF121 cDNA. Ann Surg 230: 466–470
Ross R (1993) The pathogenesis of atherosclerosis: A perspective for the 1990 s. Nature 362: 801–809
San H, Yang ZY, Pompili VJ, Jaffe ML, Plautz GE, Xu L, Feigner JH, Wheeler CJ, Feigner PL, Gao X, et al (1993) Safety and short-term toxicity of a novel cationic lipid formulation for human gene therapy. Hum Gene Ther 4: 781–788
Semsarian C, Ahmad I, Giewat M, Georgakopoulos D, Schmitt JP, McConnell BK, Reiken S, Mende U, Marks AR, Kass DA, Seidman CE, Seidman JG (2002) The L-type calcium channel inhibitor diltiazem prevents cardiomyopathy in a mouse model. J Clin Invest 109: 1013–20
Sousa JE, Costa MA, Abizaid AC, Rensing BJ, Abizaid AS, Tanajura LF, Kozuma K, Langenhove G, Sousa AG, Falotico R, Jaeger J, Popma JJ, Serruys PW (2001) Sustained suppression of neointimal proliferation by sirolimus-eluting stents: one-year angiographic and intravascular ultrasound follow-up. Circulation 104: 2007–2011
Stein CA, Cheng YC (1993) Antisense oligonucleotides as therapeutic agents — Is the bullet really magical? Science 262: 1004–1012
Svensson EC, Black HB, Dugger DL, Tripathy SK, Goldwasser E, Hao Z, Chu L, Leiden JM (1997) Long-term erythropoietin expression in rodents and non-human primates following intramuscular injection of a replication-defective adenoviral vector. Hum Gene Ther 8: 1797–1806
Takeshita S, Weir L, Chen D, Zheng LP, Riessen R, Bauters C, Symes JF, Ferrara N, Isner JM (1996) Therapeutic angiogenesis following arterial gene transfer of vascular endothelial growth factor in a rabbit model of hindlimb ischemia. Biochem Biophys Res Commun 227: 628–635
Tripathy SK, Black HB, Goldwasser E, Leiden JM (1996) Immune responses to transgene-encoded proteins limit the stability of gene expression after injection of replication-defective adenovirus vectors. Nat Med 2: 545–550
Vale PR, Losordo DW, Milliken CE, McDonald MC, Gravelin LM, Curry CM, Esakof DD, Maysky M, Symes JF, Isner JM (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
Leyen HE, Gibbons GH, Morishita R, Lewis NP, Zhang L, Nakajima M, Kaneda Y, Cooke JP, Dzau VJ (1995) Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene. Proc Natl Acad Sci U S A 92: 1137–1141
Woffendin C, Ranga U, Yang Z, Xu L, Nabel GJ (1996) Expression of a protective gene-prolongs survival of T cells in human immunodeficiency virus-infected patients. Proc Natl Acad Sci U S A 93: 2889–2894
Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Feigner PL (1990) Direct gene transfer into mouse muscle in vivo. Science 247: 1465–1468
Yang Y, Li Q, Ertl HC, Wilson JM (1994a) Cellular immunity to viral antigens limits El-deleted adenoviruses for gene therapy. Proc Natl Acad Sci USA 91: 4407–4411
Yang Y, Nunes FA, Berencsi K, Gonczol E, Engelhardt JF, Wilson JM (1994b) Inactivation of E2a in recombinant adenoviruses improves the prospect for gene therapy in cystic fibrosis. Nat Genet 7: 362–369
Yang Y, Li Q, Ertl HC, Wilson JM (1995) Cellular and humoral immune response to viral antigens create barriers to lung-directed gene therapy with recombinant adenoviruses. J Virol 69: 2004–2015
Yang Y, Su Q, Grewal IS, Schilz R, Flavell RA, Wilson JM (1996) Transient subversion of CD40 ligand function diminishes immune responses to adenovirus vectors in mouse liver and lung tissues. J Virol 70: 6370–6377
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Nabel, G.J. (2003). The Future of Gene Therapy. In: Rubanyi, G.M., Ylä-Herttuala, S. (eds) Human Gene Therapy: Current Opportunities and Future Trends. Ernst Schering Research Foundation Workshop, vol 43. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-05352-2_1
Download citation
DOI: https://doi.org/10.1007/978-3-662-05352-2_1
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-662-05354-6
Online ISBN: 978-3-662-05352-2
eBook Packages: Springer Book Archive