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1
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0030690936
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A gene therapy approach to regulated delivery of erythropoietin as a function of oxygen tension
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of outstanding interest. This is the first example of in vivo physiologically regulated transgene expression in skeletal muscle. The authors use the murine phosphoglycerate kinase hypoxia-inducible promoter to regulate the expression of the human Epo gene.
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Rinsch C, Regulier E, Deglon N, Dalle B, Beuzard Y, Aebischer P. A gene therapy approach to regulated delivery of erythropoietin as a function of oxygen tension. of outstanding interest Hum Gene Ther. 8:1997;1881-1889 This is the first example of in vivo physiologically regulated transgene expression in skeletal muscle. The authors use the murine phosphoglycerate kinase hypoxia-inducible promoter to regulate the expression of the human Epo gene.
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Hum Gene Ther
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Rinsch, C.1
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Aebischer, P.6
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2
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0031040987
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Long-term control of erythropoietin secretion by doxycycline in mice transplanted with engineered primary myoblasts
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of outstanding interest. The authors use a modified version of the tetracycline-regulatable system described by Bujard and co-workers to regulate transgene expression in vivo. Two retroviral vectors are used to deliver the components of the regulated system to myoblasts ex vivo which are then transplanted by IM injection into mice. They demonstrate a 200-fold increase in gene expression in response to doxycycline in vitro. Most importantly, the authors demonstrate the long-term persistence, reversibility, safety and rapid modulation of this system in vivo.
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Bohl D, Naffakh N, Heard J. Long-term control of erythropoietin secretion by doxycycline in mice transplanted with engineered primary myoblasts. of outstanding interest Nat Med. 3:1997;299-305 The authors use a modified version of the tetracycline-regulatable system described by Bujard and co-workers to regulate transgene expression in vivo. Two retroviral vectors are used to deliver the components of the regulated system to myoblasts ex vivo which are then transplanted by IM injection into mice. They demonstrate a 200-fold increase in gene expression in response to doxycycline in vitro. Most importantly, the authors demonstrate the long-term persistence, reversibility, safety and rapid modulation of this system in vivo.
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Bohl, D.1
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Bohl D, Heard J. Modulation of erythropoietin delivery from engineered muscles in mice. Hum Gene Ther. 8:1997;195-204.
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Long-term expression of erythropoietin in the systemic circulation of mice after intramuscular injection of a plasmid DNA vector
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of special interest. The authors used a novel plasmid vector to demonstrate stable high-level gene expression following IM injection into skeletal muscle. This is the first example of expression of physiological levels of a secreted protein into the circulation after IM injection of plasmid DNA. It demonstrates the feasibility of naked DNA injections for human gene therapy.
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Tripathy SK, Svensson EC, Black HB, Goldwasser E, Margalith M, Hobart PM, Leiden JM. Long-term expression of erythropoietin in the systemic circulation of mice after intramuscular injection of a plasmid DNA vector. of special interest Proc Natl Acad Sci USA. 93:1996;10876-10880 The authors used a novel plasmid vector to demonstrate stable high-level gene expression following IM injection into skeletal muscle. This is the first example of expression of physiological levels of a secreted protein into the circulation after IM injection of plasmid DNA. It demonstrates the feasibility of naked DNA injections for human gene therapy.
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Tripathy, S.K.1
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Newgard CB. Cellular engineering and gene therapy strategies for insulin replacement in diabetes. Diabetes. 43:1994;341-350.
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Chen H, Mack LM, Kelly R, Ontell M, Kochanek S, Clemens PR. Persistence in muscle of an adenoviral vector that lacks all viral genes. of special interest Proc Natl Acad Sci USA. 94:1997;1645-1650 See annotation [7].
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0029857641
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of special interest. These two papers [6,7] describe the use of a novel gutted adenovirus vector that does not contain viral genes to transduce skeletal muscle in vivo. The efficiency of these vectors in skeletal myocyte transduction is comparable to first generation adenovirus vectors but only transient gene expression was achieved.
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Clemens PR, Kochanek S, Sunada Y, Chen H, Campbell KP, Caskey CT. In vivo muscle gene transfer of full-length dystrophin with an adenoviral vector that lacks all viral genes. of special interest Gene Ther. 3:1996;965-972 These two papers [6,7] describe the use of a novel gutted adenovirus vector that does not contain viral genes to transduce skeletal muscle in vivo. The efficiency of these vectors in skeletal myocyte transduction is comparable to first generation adenovirus vectors but only transient gene expression was achieved.
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Caskey, C.T.6
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8
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0030453791
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Direct intramuscular gene transfer of naked DNA encoding vascular endothelial growth factor augments collateral development and tissue perfusion
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Tsurumi Y, Takeshita S, Chen D, Kearney M, Rossow ST, Passeri J, Horowitz JR, Symes JF, Isner JM. Direct intramuscular gene transfer of naked DNA encoding vascular endothelial growth factor augments collateral development and tissue perfusion. Circulation. 94:1996;3281-3290.
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Passeri, J.6
Horowitz, J.R.7
Symes, J.F.8
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9
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0030902985
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Herzog RW, Hagstrom JN, Kung S, Tai SJ, Wilson JM, Fisher KJ, High KA. Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adeno-associated virus. Proc Natl Acad Sci USA. 94:1997;5804-5809.
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Takeshita S, Isshiki T, Sato T. Increased expression of direct gene transfer into skeletal muscles observed following acute ischemic injury in rats. Lab Invest. 75:1996;487-502.
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of special interest. The authors summarize previous work on muscle-based gene therapy and describe candidate diseases for human muscle gene therapy.
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Svensson EC, Tripathy SK, Leiden JM. Muscle-based gene therapy: realistic possibilities for the future. of special interest Mol Med Today. 2:1996;166-172 The authors summarize previous work on muscle-based gene therapy and describe candidate diseases for human muscle gene therapy.
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Doh SG, Vahlsing HL, Hartikka J, Liang X, Manthorpe M. Spatial-temporal patterns of gene expression in mouse skeletal muscle after injection of lacZ plasmid DNA. Gene Ther. 4:1997;648-663.
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Wells KE, Maule J, Kingston R, Foster K, McMahon J, Damien E, Poole A, Wells DJ. Immune responses, not promoter inactivation, are responsible for decreased long-term expression following plasmid gene transfer into skeletal muscle. FEBS Letters. 407:1997;164-168.
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of special interest. The authors describe the construction of a novel plasmid DNA vector with increased transcriptional efficiency for muscle-based gene therapy.
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Hartikka J, Sawdey M, Cornefert-Jensen F, Margalith M, Barnhart K, Nolasco M, Vahlsing HL, Meek J, Marquet M, Hobart P, et al. An improved plasmid DNA expression vector for direct injection into skeletal muscle. of special interest Hum Gene Ther. 7:1996;1205-1217 The authors describe the construction of a novel plasmid DNA vector with increased transcriptional efficiency for muscle-based gene therapy.
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Vahlsing, H.L.7
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of outstanding interest. This paper provides a detailed analysis of the immune responses following IM injection of first generation adenovirus vectors. The authors show that cellular and humoral immune responses against foreign transgene proteins are predominantly responsible for the transient transgene expression seen after IM injection of first generation adenovirus vectors. In addition, they demonstrate long-term expression following a single IM injection of an adenovirus vector encoding a self transgene.
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Tripathy SK, Black HB, Goldwasser E, Leiden JM. Immune responses to transgene-encoded proteins limit the stability of gene expression after injection of replication-defective adenovirus vectors. of outstanding interest Nat Med. 2:1996;545-550 This paper provides a detailed analysis of the immune responses following IM injection of first generation adenovirus vectors. The authors show that cellular and humoral immune responses against foreign transgene proteins are predominantly responsible for the transient transgene expression seen after IM injection of first generation adenovirus vectors. In addition, they demonstrate long-term expression following a single IM injection of an adenovirus vector encoding a self transgene.
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of special interest. These two papers [27,28] document stable expression of transgenes following IM injection of AAV vectors into immunocompetent mice. Transgene expression was observed up to 1.5 years. These data suggest that AAV will be a promising vector for human muscle-based gene therapy.
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Xiao X, Li J, Samulski RJ. Efficient long-term gene transfer into muscle tissue of immunocompetent mice by Adeno-associated virus vector. of special interest J Virol. 70:1996;8098-8108 These two papers [27,28] document stable expression of transgenes following IM injection of AAV vectors into immunocompetent mice. Transgene expression was observed up to 1.5 years. These data suggest that AAV will be a promising vector for human muscle-based gene therapy.
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