The introduction and expression of exogenous genetic material in cultu
red cells has provided a powerful tool for studying gene function and
regulation. Immortalized cell lines have been useful for establishing
gene transfer methodologies that are generally inefficient. For invest
igators of epidermal and mucosal biology, wishing to make use of the t
issue architecture produced by primary keratinocytes in vitro, the lim
ited life span of these cells presents a host of unique problems. Prim
ary cells require the use of gene transfer methods that are highly eff
icient and will not significantly alter the cell's normal differentiat
ion pathway. The purpose of this review is to evaluate gene transfer t
echnology as it applies to keratinocytes.