Lentivirus-mediated gene transfer to human epidermis

The Journal of Investigative Dermatology. Symposium Proceedings
S GhazizadehLorne B Taichman

Abstract

For long-term cutaneous gene therapy, the therapeutic gene must be targeted to stem cells and be stably transmitted to and expressed in descendant cells. Retroviral vectors are highly efficient in gene transfer to human keratinocyte stem cells in culture; however, they cannot transduce quiescent stem cells in vivo. As lentiviral vectors (LVV) transduce non-proliferating cells, their ability to target human epidermal stem cells was evaluated. LVV were highly efficient in gene transfer to clonogenic keratinocytes in vitro. Despite higher transgene DNA content and comparable levels of transgene mRNA, levels of transgene product directed by lentivectors were 3-folds lower than that of retrovectors. When transduced keratinocytes were grafted onto mice, transgene expression persisted for at least 20 wk; however, transgene product was detected primarily in the uppermost layers of epidermis. Inclusion of an element that is known to facilitate nuclear export of intron-less transcripts, resulted in enhanced transgene expression in keratinocytes. In vivo transduction of xenografted human skin with these vectors resulted in efficient gene transfer to epidermal progenitor cells. These results demonstrate stem cell transduction by LVV and po...Continue Reading

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Citations

Nov 10, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Emilie WarrickThierry Magnaldo
Mar 16, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Zhenmei Lu, Soosan Ghazizadeh
May 8, 2008·Journal de la Société de biologie·Emilie WarrickThierry Magnaldo
Feb 22, 2008·Human Gene Therapy·Nikolai KunicherAmos Panet
May 25, 2012·The Journal of Investigative Dermatology·Sirpa AhoCarol A Bosko
Jan 29, 2005·The Journal of Investigative Dermatology·Soosan Ghazizadeh, Lorne B Taichman
Feb 23, 2012·Scientific Reports·Emilio González-GonzálezRoger L Kaspar
Mar 25, 2015·The Journal of Biological Chemistry·Vladislav RyvkinSoosan Ghazizadeh
Aug 28, 2020·Nature Communications·Shuxiong WangScott X Atwood
Sep 26, 2020·Journal of Internal Medicine·B M Lichtenberger, M Kasper

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