The cytokine interferon-gamma (IFN-gamma), initiates both cell cycle a
rrest and cell death in certain cell lines. Through a novel strategy o
f cell transfection with episomal vectors expressing antisense cDNAs,
Deiss et al.((1,2)) have demonstrated that it is possible to isolate g
enes that are required for the initiation of cell death by the cytokin
e IFN-gamma. This approach, referred to as TKO, for Technical Knock Ou
t, has identified several genes whose activity appears to be essential
for the induction of apoptosis by IFN-gamma in HeLa cells. interestin
gly these genes appear to mediate IFN-gamma-induced apoptosis in HeLa
cells, but their inhibition by antisense does not ameliorate the anti-
proliferative effects of lFN-gamma in these cells. The clever strategy
employed by these authors holds promise for others who wish to isolat
e genes required for other differentiative processes in cultured cell
lines.