Gene transfer in human skin with different pseudotyped HIV-based vectors

Akira Hachiya, P. Sriwiriyanont, A. Patel, N. Saito, A. Ohuchi, T. Kitahara, Y. Takema, R. Tsuboi, R. E. Boissy, M. O. Visscher, W. M. James, G. P. Kobinger

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)648-656
Number of pages9
JournalGene Therapy
Volume14
Issue number8
DOIs
StatePublished - Apr 2007
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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