Cell fate conversion by conditionally switching the signal-transducing domain of signalobodies



Conditionally and strictly controlling cell fates is important for biomedical applications including cell therapies. Although previous studies have been based on regulating the expression or activation of signaling molecules, the techniques therein require improvement in terms of reducing leakiness and complexity. In this study, we propose a novel cell fate converting system using our previously developed antibody/receptor chimeras named “signalobodies” in combination with a Cre/loxP recombination system. We designed a “switch vector” where a growth signalobody gene was flanked by two loxP sites and a death signalobody gene was placed downstream of the floxed cassette. Cells transduced with the switch vector showed superior growth activity in the presence of a specific antigen. Subsequent expression of Cre induced the death signalobody, leading to conditional cell death. This technology could be applicable for other cell fate conversion systems including differentiation and migration, by using appropriate signal-transducing domains. Biotechnol. Bioeng. 2013;110: 3219–3226. © 2013 Wiley Periodicals, Inc.