ELIZABETH S . FENJVES , JONATHAN SMITH , ' SANDY ZARADIC , and LORNE B

Grafts of autologous keratinocytes genetically altered to secrete a new gene product are a potential vehicle for gene therapy. T o consider the feasibility of such an approach, w e have examined the ability of keratinocytes to secrete and deliver apolipoprotein E (apoE) to the circulation of mice bearing grafts of h u m a n keratinocytes. The grafted keratinocytes secreted two forms of apoE, an endogenous apoE encoded in the genome and a recombinant apoE encoded in a transfected gene construct. In vitro studies showed that endogenous apoE was secreted from basal keratinocytes whereas recombinant apoE was secreted from basal as well as suprabasal cells. O n the basis of amounts of recombinant apoE present in the serum of grafted mice, w e estimate that a graft occupying 2 % of the surface area of an adult h u m a n would deliver 6.5-8.3 m g of recombinant apoE