The intracellular expression of antibodies in mammalian cells is a strategy
to inhibit the in vivo function of selected molecules but is limited by th
e unpredictable behaviour of antibodies when intracellularly expressed, Rec
ent advances in the field of antibody expression in Escherichia coli show t
hat the introduction of mutations can improve the properties of some antibo
dy domains, but the general applicability of this approach to intracellular
antibodies remains to be proved. As a complement to rational approaches, w
e describe selection schemes in which antibodies are selected on the basis
of their performance in vivo as intracellular antibodies.