Abstract
Human gene therapy has been both a disappointment and a triumph. It has disappointed in the sense that the early promise of safe and efficient treatment and cure of human disease has not come to pass several years after the first introduction of DNA into patients for therapeutic purposes. It has been a triumph because it has captured the creative energies and imagination of thousands of scientists throughout the world, has garnered extensive investment by governments, non—profit research foundations, and the private sector, and has provided a rational outlet for translation of discoveries in basic biology to the prevention, treatment, and cure of human disease.
“Ah, but a man’s reach should exceed his grasp, or what’s a heaven for!”
Robert Browning, 1855
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
Aksentijevich I, Cardarelli CO, Pastan I, Gottesman MM (1996) Retroviral transfer of the human MDR1 gene confers resistance to bisantrene-specific hematotoxicity. Clin Cancer Res 2:973–980
Amara JF, Clackson T, Rivera VM, Guo T, Keenan T, Natesan S, Pollock R, Yang W, Courage NL, Holt DA, Gilman M (1997) A versatile synthetic dimerizer for the regulation of protein-protein interactions. Proc Natl Acad Sci USA 94:10618–10623
Anderson WF (1995) Gene therapy. Sci Am 273:124–128
Baudard M, Flotte TR, Aran JM, Thierry AR, Pastan I, Gottesman MM (1996) Expression of the human multidrug resistance and glucocerebrosidase cDNAs from adeno-associated vectors: efficient promoter activity of AAV sequences and in vivo delivery via liposomes. Hum Gene Ther 7:1309–1322
Blaese RM, Culver KW, Miller AD, Carter CS, Fleisher T, Clerici M, Shearer G, Chang L, Chiang Y, Tolstoshev P, Greenblatt JJ, Rosenberg SA, Klein H, Berger M, Mullen CA, Ramsey WJ, Muul L., Morgan RA, Anderson WF (1995) T lymplocyte-directed gene therapy for ADA-SCID: initial trial results after 4 years. Science 270:475–480
Bonadonna G, Valagussa P, Brambilla C, Ferrari L, Moliterni A, Terenziani M, Zambetti M (1998) Primary chemotherapy in operable breast cancer: eight-year experience at the Milan Cancer Institute. J Clin Oncol 16:93–100
Brady RO, Barton NW (1996) Enzyme replacement and gene therapy for Gaucher’s disease. Lipids 31 [Suppl]:S137-S139
Brenner MK (1996) Gene transfer to hematopoietic cells. N Engl J Med 335:337–339
Fink DJ, Glorioso J (1997) Engineering herpes simplex virus vectors for gene transfer to neurons. Nat Med 3:357–359
Flasshove M, Banerjee D, Leonard JP, Mineishi S, Li M-X, Bettino JR, Moore MAS (1998) Retroviral transduction of human CD34+ umbilical cord blood progenator cells with a mutated dihydrofolate reductase cDNA. Hum Gene Ther 9:63–71
Galski H, Sullivan M, Willingham MC, Chin K-V, Gottesman MM, Pastan I, Merlino GT (1989) Expression of a human multidrug-resistance cDNA (MDR1) in the bone marrow of transgenic mice: resistance to daunomycin-induced leukopenia. Mol Cell Biol 9:4357–4363
Gao X, Huang L (1995) Cationic liposome-mediated gene transfer. Gene Ther 2:710–722
Gottesman MM, Hrycyna CA, Schoenlein PV, Germann UA, Pastan I (1995) Genetic analysis of the multidrug transporter. Annu Rev Genet 29:607–649
Grignani F, Kinsella T, Mencarelli A, Valtieri M, Riganelli D, Grignani F, Lanfrancone L, Peschle C, Nolan GP, Pelicci PG (1998) High-efficiency gene transfer and selection of human hematopoietic progenitor cells with a hybrid EBV/retroviral vector expressing the green fluorescence protein. Cancer Res 58:14–19
Jain RK (1994) Barriers to drug delivery in solid tumors. Sci Am 271:58–65
Kong H-L, Crystal RG (1998) Gene therapy strategies for tumor antiangio-genesis. J Natl Cancer Inst 90:273–286
Lee CGL, Jeang K-T, Martin MA, Pastan I, Gottesman MM (1997) Efficient long-term co-expression of a hammerhead ribozyme tartgeted to the U5 region of HIV-1 LTR by linkage to the multidrug-resistance gene. Antisense Nucl Acid Drug Dev 7:511–522
Malech HL, Maples PB, Whiting-Theobald N, Linton GF, Sekhsaria S, Vowells SJ, Li F, Miller JA, DeCarlo E, Holland SM, Leitman SF, Carter CS, Butz RE, Read EJ, Fleisher TA, Schneiderman RD, Van Epps DE, Spratt SK, Maack CA, Rokovich JA, Cohen LK, Gallin JI (1997) Prolonged production of NADPH oxidase-corrected granulocytes after gene therapy of chronic granulomatous disease. Proc Natl Acad Sci USA 94:12133–12138
Murphy JE, Zhou S, Giese K, Williams LT, Escobedo JA, Dwarki VJ (1997) Long-term correction of obesity and diabetes in genetically obese mice by a single intramuscular injection of recombinant adeno-associated virus encoding mouse leptin. Proc Natl Acad Sci USA 94:13921–13926
Orkin SH, Motulsky AG, co-chairs (1995) Report and recommendations of the panel to access the NIH investment in research on gene therapy. National Institutes of Health, Bethesda MD, http://www.nih.gov/news/panelrep.html
Ram Z, Culver KW, Walbridge S, Blaese RM, Oldfield EH (1993) In situ retroviral-mediated gene transfer for the treatment of brain tumors in rats. Cancer Res 53:83–88
Robertson ES, Ooka T, Kieff ED (1996) Epstein-Barr virus vectors for gene delivery to B lymphocytes. Proc Natl Acad Sci USA 93:11334–11340
Rosenberg SA (1997) Cancer vaccines based on the identification of genes encoding cancer regression antigens. Immunol Today 18:175–182
Roth JA, Cristiano RJ (1997) Gene therapy for cancer: what have we done and where are we going? J Natl Cancer Inst 89:21–39
Rund D, Dagan M, Dalyot N, Kimchi-Sarfaty C, Schoenlein P, Gottesman MM, Oppenheim A (1998) Efficient transduction of human hematopoietic cells with the human multidrug resistance gene 1 (MDR1) via SV40 pseudovirions. Hum Gene Ther 9:649–657
Sandalon Z, Dalyot-Herman H, Oppenheim AB, Oppenheim A (1997) In vitro assembly of SV40 virions and pseudovirions: vector development for gene therapy. Hum Gene Ther 8:843–849
Sidransky E, Fartasch M, Lee RE, Metlay LA, Abella S, Zimran A, Gao W, Elias PM, Ginns EI, Holleran WM (1996) Epidermal abnormalities may distinguish type 2 from type 1 and type 3 of Gaucher disease. Pediatr Res 39:134–141
Sorrentino BP, Brandt SJ, Bodine D, Gottesman MM, Pastan I, Cline A, Nienhuis AW (1992) Retroviral transfer of the human MDR1 gene permits selection of drug resistant bone marrow cells in vivo. Science 257:99–103
Wang G, Levy DD, Seidman MM, Glazer PM (1995) Targeted mutagenesis in mammalian cells mediated by intracellular triple helix formation. Mol Cell Biol 15:1759–1768
Wang G, Seidman MM, Glazer PM (1996) Mutagenesis in mammalian cells induced by triple helix formation and transcription-coupled repair. Science 271:802–805
Zhao RC, McIvor RS, Griffin JD, Verfaillie CM (1997) Gene therapy for chronic myelogenous leukemia (CML): a retroviral vector that renders hematopoietic progenitors, methotrexate-resistant and CML progenitors functionally normal and nontumorigenic in vivo. Blood 90:4687–4698
Editor information
Rights and permissions
Copyright information
© 1998 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Gottesman, M.M. (1998). Human Gene Therapy: Future Prospects. In: Sobol, R.E., Scanlon, K.J., Nestaas, E. (eds) Gene Therapy. Ernst Schering Research Foundation Workshop, vol 27. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-03577-1_1
Download citation
DOI: https://doi.org/10.1007/978-3-662-03577-1_1
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-662-03579-5
Online ISBN: 978-3-662-03577-1
eBook Packages: Springer Book Archive