Gene delivery to the hair follicle.

Skin and appendages such as hair follicles are attractive candidates for gene therapy targets because they are easily accessible and can be removed and genetically manipulated in culture. Hair follicles are of special interest because our understanding of hair follicle biology and pathophysiology has progressed significantly in recent years, and we now have a much better understanding of how genes, encoding transcription factors, growth factors, and cytokines regulate both hair follicle development and the cycles of hair follicle growth (anagen, catagen, and telogen) (Cotsarelis and Millar, 2001; Millar, 2002). Also important is the characterization of an increasing number of genetic mutations that affect hair growth and can result in hair loss (Cotsarelis and Millar, 2001). Gene therapy could be used to introduce genes that manipulate hair follicle growth and cycling or that replace the mutated defective gene with a normal wild-type gene. As our understanding of the polygenic basis for a number of alopecias improves, gene-based therapies might also be designed to provide more promising treatments than current palliative therapies for hair loss. This review will describe some of the recent progress in gene delivery to hair follicles and discuss examples of how gene delivery can cause phenotypic changes in hair follicles.