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R. Scott McIvor,
Associate Dept. Head
College of Biological Sciences, Medical School
Phone: (612) 626-1497
Research Interests: Gene therapy
The general research interest of Dr. McIvor's laboratory is gene therapy for genetic diseases and cancer. Specific research activities include: (i) Use of recombinant retroviral vectors for gene transfer into hematropoietic stem cells in the treatment of cancer and inherited disorders such as immunodeficiency diseases and lysosomal storage diseases; (ii) Introduction of drug-resistance genes into normal hematopoietic cells to protect against the toxic side effects of cancer chemotherapy; (iii) Use of adeno-associated virus for treatment of storage diseases and as a vector for gene transfer into the central nervous system in the treatment of neurological disorders; (iv) Adaptation of a novel vertebrate transposon ("Sleeping Beauty") to viral and non-viral delivery systems for gene therapy.
Selected Recent Publications
- Bell JB, Podetz-Pedersen KM, Aronovich EL, Belur LR, McIvor RS, Hackett PB. 2007. Preferential delivery of the Sleeping Beauty transposon system to livers of mice by hydrodynamic injection. Nat Protoc.2(12):3153-65.
- Belur LR, Podetz-Pedersen K, Frandsen J, McIvor RS. 2007. Lung-directed gene therapy in mice using the nonviral Sleeping Beauty transposon system. Nat Protoc. 2(12):3146-52.
- Wilber A, Linehan JL, Tian X, Woll PS, Morris JK, Belur LR, McIvor RS, Kaufman DS. 2007. Efficient and stable transgene expression in human embryonic stem cells using transposon-mediated gene transfer. Stem Cells. 25(11):2919-27.
- Gori JL, Podetz-Pedersen K, Swanson D, Karlen AD, Gunther R, Somia NV, McIvor RS. 2007.Protection of mice from methotrexate toxicity by ex vivo transduction using lentivirus vectors expressing drug-resistant dihydrofolate reductase. J Pharmacol Exp Ther. 322(3):989-97.
- Zayed H, Xia L, Yerich A, Yant SR, Kay MA, Puttaraju M, McGarrity GJ, Wiest DL, McIvor RS, Tolar J, Blazar BR. 2007. Correction of DNA Protein Kinase Deficiency by Spliceosome-mediated RNA Trans-splicing and Sleeping Beauty Transposon Delivery. Mol Ther. 15(7):1273-9.
- Wilber A, Wangensteen KJ, Chen Y, Zhuo L, Frandsen JL, Bell JB, Chen ZJ, Ekker SC, McIvor RS, Wang X. 2007. Messenger RNA as a Source of Transposase for Sleeping Beauty Transposon-mediated Correction of Hereditary Tyrosinemia Type I. Mol Ther. 15(7):1280-1287.
- Aronovich EL, Bell JB, Belur LR, Gunther R, Koniar B, Erickson DC, Schachern PA, Matise I, McIvor RS, Whitley CB, Hackett PB. 2007. Prolonged expression of a lysosomal enzyme in mouse liver after Sleeping Beauty transposon-mediated gene delivery: implications for non-viral gene therapy of mucopolysaccharidoses. J Gene Med. 9(5):403-15.
- Balciunas D, Wangensteen KJ, Wilber A, Bell J, Geurts A, Sivasubbu S, Wang X, Hackett PB, Largaespada DA, McIvor RS, Ekker SC. 2006. Harnessing a high cargo-capacity transposon for genetic applications in vertebrates. PLoS Genet. 2(11):e169.
- Tolar J, Nauta AJ, Osborn MJ, Panoskaltsis Mortari A, McElmurry RT, Bell S, Xia L, Zhou N, Riddle M, Schroeder TM, Westendorf JJ, McIvor RS, Hogendoorn PC, Szuhai K, Oseth L, Hirsch B, Yant SR, Kay MA, Peister A, Prockop DJ, Fibbe WE, Blazar BR. 2007. Sarcoma derived from cultured mesenchymal stem cells. Stem Cells. 25(2):371-9.
- Geurts AM, Wilber A, Carlson CM, Lobitz PD, Clark KJ, Hackett PB, McIvor RS, Largaespada DA. 2006. Conditional gene expression in the mouse using a Sleeping Beauty gene-trap transposon. BMC Biotechnol. 6:30.
- O'Brien TA, Tuong DT, Basso LM, McIvor RS, Orchard PJ. 2006. Coexpression of the uracil phosphoribosyltransferase gene with a chimeric human nerve growth factor receptor/cytosine deaminase fusion gene, using a single retroviral vector, augments cytotoxicity of transduced human T cells exposed to 5-fluorocytosine. Hum Gene Ther. 17(5):518-30.
- Zayed, H., R.S. McIvor, D.L. Wiest, and B.R. Blazar. 2006. In vitro functional correction of the mutation responsible for murine severe combined immune deficiency by short fragment homologous recombination. Hum. Gene Ther. 17: 158-166.
- Wilber, A.C., J.L. Frandsen, J.L. Geurts, D.A. Largaespada, P.B. Hackett, and R.S. McIvor. 2006. RNA as a source of transposase for Sleeping Beauty-mediated gene insertion and expression in somatic cells and tissues. Mol. Ther. 13: 625-630.
- Score, P.R., L. Belur, J.L. Frandsen, J.L. Geurts, P.B. Hackett, D.A. Largaespada, and R.S. McIvor. 2006. Sleeping Beauty-mediated transposition and long-term expression in vivo: application of the LoxP-Cre recombinase system for transposon-specific expression. Mol. Ther. 13: 617-624.
- Huang, X, A.C. Wilber, L. Bao, D. Tuong, J. Tolar, P.J. Orchard, B.L. Levine, C.H. June, R.S. McIvor, B.R. Blazar, and X. Zhou. 2006. Stable gene transfer and expression in human primary T-cells by the Sleeping Beauty transposon system. Blood 107: 483-491.
- Seth, G., R.S. McIvor, and W.-S. Hu. 2006. 17b-hydroxysteroid dehydrogenase type 7 (Hsd17b7) reverts cholesterol auxotrophy in NS0 cells. J. Biotechnol. 121: 241-252.
- Carlson, C.M., J.L. Frandsen, R.S. McIvor, and D.A. Largaespada. 2005. Somatic integration of an oncogene-harboring Sleeping Beauty transposon to model tumors in the mouse. Proc. Natl Acad. Sci. USA 102: 17059-17064.
- Wilber, A.C., J.L. Frandsen, K. Wangensteen, S.C. Ekker, X. Wang and R.S. McIvor. 2005. Dynamic gene expression following systemic delivery of plasmid DNA as determined by in vivobioluminescent imaging. Hum. Gene Ther. 16: 1325.
- Zhang J.L., J. Cai, J.D. Jackson, C.A. Kuszynski, S. Walls, R.S. McIvor, and I.J. Fox. 2005. Long-term transgene expression and survival of transgene-expressing grafts following lentivirus transduction of bone marrow side population cells. Transplantation 79:882-888.
- Belur, L., R.I. James, C. May, M.D. Diers, D. Swanson, R. Gunther and R.S. McIvor. 2005. Methotrexate preconditioning allows sufficient engraftment to confer drug resistance in mice transplanted with marrow expressing drug-resistant dihydrofolate reductase activity. J. Pharmacol. Exp. Ther. 314: 668-674.
- Osborn, M.J., A. Panoskaltsis-Mortari, R.T. McElmurry, S.K. Bell, D.A.A. Vignali, M.D. Ryan, A.C. Wilber, R.S. McIvor, J. Tolar, and B.R. Blazar. 2005. A picornaviral 2A-like sequence-based tricistronic vector allowing for high-level therapeutic gene expression coupled to a dual-reporter system. Mol. Ther. 12:569-574.
- Ohlfest, J.R, J.L. Frandsen, S.Fritz, P.D. Lobitz, S.G. Perkinson, K.J. Clark, G. Nelsestuen, N.S. Key, R.S. McIvor, P.B. Hackett and D.A. Largaespada. 2005. Phenotypic correction and long-term expression of factor VIII in hemophilic mice by immunotolerization and nonviral gene transfer using the Sleeping Beauty transposon system. Blood. 105(7):2691-8.
- Belur, L., and R.S. McIvor. 2004. Delivery of transposon DNA to lungs of mice using polyethyleneimine-DNA complexes. In: Gene Delivery to Mammalian Cells: Volume 1: Nonviral Gene Transfer Techniques. Ed., W.C. Heiser. Methods in Molecular Biology 245: 137-143.
- Sweeney, C.L, and R.S. McIvor. 2004. Drug-resistance gene transfer as an antitumor strategy. In Cancer Gene Therapy, Ed. D. Curiel and J. Douglas, Humana Press, P. 321-333.
- Hartung, S.D., J.S. Frandsen, D. Pan, B. Koniar, P. Graupman, R. Gunther, W.C. Low, C.B. Whitley and R. S. McIvor. 2004. Correction of metabolic, neurologic, and craniofacial abnormalities in MPS I mice treated at birth with adeno-associated virus vector transducing the human alpha-L-iduronidase gene. Molecular Therapy, 9: 866-875.
- Belur, L., J.L. Frandsen, A. Dupuy, D.L. Largaespada, P.B. Hackett and R.S. (2003)McIvor. Integration and long-term expression in lung mediated by the Sleeping Beauty transposon system. Molecular Therapy 8:501-507.
- Sweeney, C.L., J.L. Frandsen, C.M. Verfaillie and R.S. McIvor. Trimetrexate inhibits progression of the murine 32Dp210 model of chronic myeloid leukemia in animals expressing drug-resistant dihydrofolate reductase. Cancer Research, 63: 1304-10.
- Warlick, C.A., M.D. Diers, J.E. Wagner and R.S. McIvor. 2002. In vivo selection of antifolate-resistant transgenic hematopoietic stem cells in a murine bone marrow transplant model. J. Pharmacol. Exptl. Therapeut. 300: 50-56.
- Belur, L., D. Boelk-Galvan, M.D.Diers, R.S. McIvor and C.L. Zimmerman. 2001. Methotrexate accumulates to similar levels in animals transplanted with normal vs. drug-resistant dihydrofolate reductase transgenic marrow.
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