title: A library of programmable DNAzymes that operate in a cellular environment.
abstract: DNAzymes were used as inhibitory agents in a variety of experimental disease settings, such as cancer, viral infections and even HIV. Drugs that become active only upon the presence of preprogrammed abnormal environmental conditions may enable selective molecular therapy by targeting abnormal cells without injuring normal cells. Here we show a novel programmable DNAzyme library composed of variety of Boolean logic gates, including YES, AND, NOT, OR, NAND, ANDNOT, XOR, NOR and 3-input-AND gate, that uses both miRNAs and mRNAs as inputs. Each gate is based on the c-jun cleaving Dz13 DNAzyme and active only in the presence of specific input combinations. The library is modular, supports arbitrary inputs and outputs, cascadable, highly specific and robust. We demonstrate the library's potential diagnostic abilities on miRNA and mRNA combinations in cell lysate and its ability to operate in a cellular environment by using beacon-like c-jun mimicking substrate in living mammalian cells.
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Kahan-Hanum
authors.forename: Yehonatan
authors.initials: Y
authors.lastname: Douek
authors.forename: Rivka
authors.initials: R
authors.lastname: Adar
authors.forename: Ehud
authors.initials: E
authors.lastname: Shapiro
mesh_terms: D045744:Cell Line, Tumor; D039301:Computers, Molecular; D021881:DNA, Catalytic / Q000235:genetics* / Q000378:metabolism*; D015723:Gene Library; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D021881:DNA, Catalytic; C485475:Dz13 DNAzyme; D035683:MicroRNAs; D012333:RNA, Messenger; D048031:JNK Mitogen-Activated Protein Kinases