A tumor specific single chain antibody dependent gene expression system

The design of conditional gene expression systems restricted to given tissu es or cellular types is an important issue of gene therapy. Systems based o n the targeting of molecules characteristic of the pathological state of ti ssues would be of interest. We have developed a synthetic transcription fac tor by fusing a single chain antibody (scFv) directed against p53 with the bacterial tetracycline repressor as a DNA binding domain. This hybrid prote in binds to p53 and can interact with a synthetic promoter containing tetra cycline-operator sequences. Gene expression can now be specifically achieve d in tumor cells harboring an endogenous mutant p53 but not in a wild-type p53 containing tumor cell line or in a non-transformed cell line, Thus, a f unctional transactivator centered on single chain antibodies can be express ed intracellularly and induce gene expression in a scFv-mediated specific m anner. This novel class of transcriptional transactivators could be referre d as 'trabodies' for transcription-activating-antibodies. The trabodies tec hnology could be useful to any cell type in which a disease related protein could be the target of specific antibodies.