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Lentivirus-mediated gene transfer to human epidermis
Soosan Ghazizadeh1, Anne B Katz, Robin Harrington
1Department of Oral Biology and Pathology, Stony Brook University, Stony Brook, New York, USA. sg2163@columbia.edu
The Journal of Investigative Dermatology. Symposium Proceedings
|September 17, 2004
Summary
Lentiviral vectors (LVV) efficiently transduce human epidermal stem cells for gene therapy. Modified LVV enhance transgene expression, enabling sustained gene delivery to skin progenitor cells.
Area of Science:
- Biotechnology
- Dermatology
- Gene Therapy
Background:
- Long-term cutaneous gene therapy requires targeting stem cells for stable gene expression.
- Retroviral vectors are effective for human keratinocyte stem cells in culture but not quiescent in vivo stem cells.
Purpose of the Study:
- To evaluate lentiviral vectors (LVV) for targeting human epidermal stem cells.
- To assess the efficiency of LVV for gene transfer and sustained expression in skin.
Main Methods:
- Assessed LVV gene transfer efficiency in clonogenic keratinocytes in vitro.
- Grafted transduced keratinocytes onto mice to evaluate in vivo transgene expression.
- Modified LVV with an element to facilitate nuclear export of intron-less transcripts.
- Evaluated in vivo transduction of xenografted human skin.
Main Results:
- LVV demonstrated high efficiency in gene transfer to keratinocytes in vitro.
- Transgene expression persisted for at least 20 weeks in grafted skin, primarily in superficial layers.
- Enhanced transgene expression was achieved using modified LVV with nuclear export elements.
- LVV enabled efficient gene transfer to epidermal progenitor cells in vivo.
Conclusions:
- Lentiviral vectors can transduce human epidermal stem cells.
- Modified LVV offer utility for direct gene transfer and sustained expression in human epidermis.
- LVV represent a promising tool for cutaneous gene therapy applications.