AntiCancer, Inc., San Diego, CA
Department of Dermatology, Kitasato University School of Medicine, Sagamihara, Japan
Study Information and Results
A novel gene therapy technology of hair follicles has been developed which results for the first time in efficient genetic and phenotype alteration of the hair shaft. Mouse anagen skin fragments in histoculture were transduced at high efficiency by adenoviral-green fluorescent protein (GFP) with subsequent grafting of the skin fragments to nude mice.
The histocultured skin fragments were treated with collagenase which made the hair follicles accessible to adenoviral-GFP enabling high-efficiency transduction. On day-1 after gene transduction, adenoviral-green fluorescent protein was expressed in 80% of hair follicles in the collagenase-treated histocultured skin. Adenoviral-green fluorescent protein was visualized in the hair bulbs and dermal papillae in the histocultured skin. Without collagenase treatment, adenoviral-green fluorescent protein expression was negligible.
The extent of adenoviral-green fluorescent protein expression in the hair follicle depended on adenoviral titer and duration of adenoviral treatment. High GFP expression was maintained for at least 18 days in histoculture. After transplantation of the GFP-transduced skin to nude mice, GFP was readily visualized in as many as 75% of hair follicles including large numbers of GFP-fluorescent growing hair shafts.
Thus, transgene expression was maintained in vivo in hair follicles to the extent that growing hair shafts were transformed as demonstrated by their specific adenoviral-green fluorescent protein fluorescence. RT-PCR confirmed GFP-gene transfer and expression in the hair follicle in histoculture as well as after grafting for at least 2 weeks.
These experiments thus demonstrate that hair follicle gene targeting ex vivo enable for the first time high efficiency gene transduction which results in extensive hair shaft alteration in vivo. This novel technology indicates the possibility of efficient clinical genetic modification of the hair shaft such as during the hair transplant process.
These experiments demonstrate that it is possible to genetically modify hair follicles by removing a small number of follicle cells, introducing new genetic material, and re-implanting the engineered cells into a an organism. This process has for the first time shown the ability to transfer follicular genetic traits from one organism to another with high efficiency. The process resulted in extensive modifications to the hair shaft after having been implanted into the new organism. This new technology indicates the possibility of efficient clinical genetic modification of the hair shaft such as during a hair transplant process.