Abstract
Pseudotyping lentiviral vector with other viral surface proteins could be applied for treating genetic anomalies in human skin. In this study, the modification of HIV vector tropism by pseudotyping with the envelope glycoprotein from vesicular stomatitis virus (VSV), the Zaire Ebola (EboZ) virus, murine leukemia virus (MuLV), lymphocytic choriomeningitis virus (LCMV), Rabies or the rabies-related Mokola virus encoding LacZ as a reporter gene was evaluated qualitatively and quantitatively in human skin xenografts. High transgene expression was detected in dermal fibroblasts transduced with VSV-G-, EboZ- or MuLV-pseudotyped HIV vector with tissue irregularities in the dermal compartments following repeated injections of EboZ- or LCMV-pseudotyped vectors. Four weeks after transduction, double-labeling immunofluorescence of β-galactosidase and involucrin or integrin β1 demonstrated that VSV-G-, EboZ- or MuLV-pseudotyped HIV vector effectively targeted quiescent epidermal stem cells which underwent terminal differentiation resulting in transgene expression in their progenies. Among the six different pseudotyped HIV-based vectors evaluated, VSV-G-pseudotyped vector was found to be the most efficient viral glycoprotein for cutaneous transduction as demonstrated by the highest level of β-galactosidase expression and genome copy number evaluated by TaqMan PCR.
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References
Cao T, Wang XJ, Roop DR . Regulated cutaneous gene delivery: the skin as a bioreactor. Hum Gene Ther 2000; 11: 2297–2300.
Ghazizadeh S, Taichman LB . Virus-mediated gene transfer for cutaneous gene therapy. Hum Gene Ther 2000; 11: 2247–2251.
Khavari PA . Genetic correction of inherited epidermal disorders. Hum Gene Ther 2000; 11: 2277–2282.
Uitto J, Pulkkinen L . The genodermatoses: candidate diseases for gene therapy. Hum Gene Ther 2000; 11: 2267–2275.
Vogel JC . Nonviral skin gene therapy. Hum Gene Ther 2000; 11: 2253–2259.
Chen M, O’Toole EA, Mullenhoff M, Medina E, Kasahara N, Woodley DT . Development and characterization of a recombinant truncated type VII collagen ‘minigene’. Implication for gene therapy of dystrophic epidermolysis bullosa. J Biol Chem 2000; 275: 24429–24435.
Chen M, Kasahara N, Keene DR, Chan L, Hoeffler WK, Finlay D et al. Restoration of type VII collagen expression and function in dystrophic epidermolysis bullosa. Nat Genet 2002; 32: 670–675.
Mecklenbeck S, Compton SH, Mejia JE, Cervini R, Hovnanian A, Bruckner-Tuderman L et al. Microinjected COL7A1-PAC vector restores synthesis of intact procollagen VII in a dystrophic epidermolysis bullosa keratinocyte cell line. Hum Gene Ther 2002; 13: 1655–1662.
Ortiz-Urda S, Thuagarajan B, Keene DR, Lin Q, Fang M, Calos MP et al. Stable nonviral genetic correction of inherited human skin disease. Nat Med 2002; 8: 1166–1170.
Dellambra E, Vailly J, Pellegrini G, Bondanza S, Golisano O, Macchia C et al. Corrective transduction of human epidermal stem cells in laminin-5-dependent junctional epidermolysis bullosa. Hum Gene Ther 1998; 9: 1359–1370.
Vailly J, Gagnoux-Palacios L, Dell’Ambra E, Romero C, Pinola M, Zambruno G et al. Corrective gene transfer of keratinocytes from patients with junctional epidermolysis bullosa restores assembly of hemidesmosomes in reconstructed epithelia. Gene Ther 1998; 5: 1322–1332.
Seitz CS, Giudice GJ, Balding SD, Marinkovich MP, Khavari PA . BP180 gene delivery in junctional epidermolysis bullosa. Gene Ther 1999; 6: 42–47.
Choate KA, Medalie DA, Morgan JR, Khavari PA . Corrective gene transfer in the human skin disorder lamellar ichthyosis. Nat Med 1996; 2: 1263–1267.
Boyce ST, Ham RG . Calcium-regulated differentiation of normal human epidermal keratinocytes in chemically defined clonal culture and serum-free serial culture. J Invest Dermatol 1983; 81: 33s–40s.
Freiberg RA, Choate KA, Deng H, Alperin ES, Shapiro LJ, Khavari PA . A model of corrective gene transfer in X-linked ichthyosis. Hum Mol Genet 1997; 6: 927–933.
Setoguchi Y, Jaffe HA, Danel C, Crystal RG . Ex vivo and in vivo gene transfer to the skin using replication-deficient recombinant adenovirus vectors. J Invest Dermatol 1994; 102: 415–421.
Tang DC, Shi Z, Curiel DT . Vaccination onto bare skin. Nature 1997; 388: 729–730.
Ghazizadeh S, Harrington R, Taichman L . In vivo transduction of mouse epidermis with recombinant retroviral vectors: implications for cutaneous gene therapy. Gene Ther 1999; 6: 1267–1275.
Hengge UR, Mirmohammadsadegh A . Adeno-associated virus expresses transgenes in hair follicles and epidermis. Mol Ther 2000; 2: 188–194.
Baek SC, Lin Q, Robbins PB, Fan H, Khavari PA . Sustainable systemic delivery via a single injection of lentivirus into human skin tissue. Hum Gene Ther 2001; 12: 1551–1558.
Kuhn U, Terunuma A, Pfutzner W, Foster RA, Vogel JC . In vivo assessment of gene delivery to keratinocytes by lentiviral vectors. J Virol 2002; 76: 1496–1504.
Niwa H, Yamamura K, Miyazaki J . Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene 1991; 108: 193–199.
Mathor MB, Ferrari G, Dellambra E, Cilli M, Mavilio F, Cancedda R et al. Clonal analysis of stably transduced human epidermal stem cells in culture. Proc Natl Acad Sci USA 1996; 93: 10371–10376.
Kolodka TM, Garlick JA, Taichman LB . Evidence for keratinocyte stem cells in vitro: Long term engraftment and persistence of transgene expression from retrovirus-transduced keratinocytes. Proc Natl Acad Sci USA 1998; 95: 4356–4361.
Anderson WF . Human gene therapy. Nature 1998; 392: 25–30.
Naldini L, Blomer U, Gallay P, Ory D, Mulligan R, Gage FH et al. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 1996; 272: 263–267.
Burns JC, Friedmann T, Driever W, Burranscano M, Yee JK . 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 1993; 90: 8033–8037.
Akkina RK, Walton RM, Chen ML, Li QX, Planelles V, Chen IS . High-efficiency gene transfer into CD34+ cells with a human immunodeficiency virus type 1-based retroviral vector pseudotyped with vesicular stomatitis virus envelope glycoprotein G. J Virol 1996; 70: 2581–2585.
Reiser J, Harmison G, Kluepfel-Stahl S, Brady RO, Karlsson S, Scubert M . Transduction of nondividing cells using pseudotyped defective high-titer HIV type 1 particles. Proc Natl Acad Sci USA 1996; 93: 15266–15271.
Mochizuki H, Schwartz JP, Tanaka K, Brady RO, Reiser J . High-titer human immunodeficiency virus type 1-based vector systems for gene delivery into nondividing cells. J Virol 1998; 72: 8873–8883.
Wool-Lewis RJ, Bates P . Characterization of Ebola virus entry by using pseudotyped viruses: identification of receptor-deficient cell lines. J Virol 1998; 72: 3155–3160.
Mitrophanous K, Yoon S, Rohll J, Patil D, Wilkes F, Kim V et al. Stable gene transfer to the nervous system using a non-primate lentiviral vector. Gene Ther 1999; 6: 1808–1818.
Chan SY, Speck RF, Ma MC, Goldsmith MA . Distinct mechanisms of entry by envelope glycoproteins of Marburg and Ebola (Zaire) viruses. J Virol 2000; 74: 4933–4937.
Stitz J, Buchholz CJ, Engelstadter M, Uckert W, Bloemer U, Schmitt I et al. Lentiviral vectors pseudotyped with envelope glycoproteins derived from gibbon ape leukemia virus and murine leukemia virus 10A1. Virology 2000; 273: 16–20.
Desmaris N, Bosch A, Salaun C, Petit C, Prevost MC, Tordo N et al. Production and neurotropism of lentivirus vectors pseudotyped with lyssavirus envelope glycoproteins. Mol Ther 2001; 4: 149–156.
Kobinger GP, Weiner DJ, Yu QC, Wilson JM . Filovirus-pseudotyped lentiviral vector can efficiently and stably transduce airway epithelia in vivo. Nat Biotechnol 2001; 19: 225–230.
Lewis BC, Chinnasamy N, Morgan RA, Varmus HE . Development of an avian leukosis-sarcoma virus subgroup A pseudotyped lentiviral vector. J Virol 2001; 75: 9339–9344.
Beyer WR, Westphal M, Ostertag W, von Laer D . Oncoretrovirus and lentivirus vectors pseudotyped with lymphocytic choriomeningitis virus glycoprotein: generation, concentration, and broad host range. J Virol 2002; 76: 1488–1495.
Ghazizadeh S, Taichman LB . Organization of stem cells and their progeny in human epidermis. J Invest Dermatol 2005; 124: 367–372.
Shayakhmetov DM, Li ZY, Ni S, Lieber A . Interference with the IL-1-signaling pathway improves the toxicity profile of systemically applied adenovirus vectors. J Immunol 2005; 174: 7310–7319.
Yang ZY, Duckers HJ, Sullivan NJ, Sanchez A, Nabel EG, Nabel GJ . Identification of the Ebola virus glycoprotein as the main viral determinant of vascular cell cytotoxicity and injury. Nat Med 2000; 6: 886–889.
Medina MF, Kobinger GP, Rux J, Gasmi M, Looney DJ, Bates P et al. Lentiviral vectors pseudotyped with minimal filovirus envelopes increased gene transfer in murine lung. Mol Ther 2003; 8: 777–789.
Watson DJ, Kobinger GP, Passini MA, Wilson JM, Wolfe JH . Targeted transduction patterns in the mouse brain by lentivirus vectors pseudotyped with VSV, Ebola, Mokola, LCMV, or MuLV envelope proteins. Mol Ther 2002; 5: 528–537.
Croyle MA, Callahan SM, Auricchio A, Schumer G, Linse KD, Wilson JM et al. PEGylation of a vesicular stomatitis virus G pseudotyped lentivirus vector prevents inactivation in serum. J Virol 2004; 78: 912–921.
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Hachiya, A., Sriwiriyanont, P., Patel, A. et al. Gene transfer in human skin with different pseudotyped HIV-based vectors. Gene Ther 14, 648–656 (2007). https://doi.org/10.1038/sj.gt.3302915
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DOI: https://doi.org/10.1038/sj.gt.3302915
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