title: Multi-input RNAi-based logic circuit for identification of specific cancer cells.
abstract: Engineered biological systems that integrate multi-input sensing, sophisticated information processing, and precisely regulated actuation in living cells could be useful in a variety of applications. For example, anticancer therapies could be engineered to detect and respond to complex cellular conditions in individual cells with high specificity. Here, we show a scalable transcriptional/posttranscriptional synthetic regulatory circuit--a cell-type "classifier"--that senses expression levels of a customizable set of endogenous microRNAs and triggers a cellular response only if the expression levels match a predetermined profile of interest. We demonstrate that a HeLa cancer cell classifier selectively identifies HeLa cells and triggers apoptosis without affecting non-HeLa cell types. This approach also provides a general platform for programmed responses to other complex cell states.
authors: Faculty of Arts and Sciences (FAS) Center for Systems Biology, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
authors: Zhen
authors: Z
authors: Xie
authors: Liliana
authors: L
authors: Wroblewska
authors: Laura
authors: L
authors: Prochazka
authors: Ron
authors: R
authors: Weiss
authors: Yaakov
authors: Y
authors: Benenson
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor; D002460:Cell Line; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D058615:Synthetic Biology / Q000379:methods; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: C494826:BAX protein, human; D014408:Biomarkers, Tumor; D035683:MicroRNAs; D051028:bcl-2-Associated X Protein