title: Nitroreductase-activatable morpholino oligonucleotides for in vivo gene silencing.
abstract: Phosphorodiamidate morpholino oligonucleotides are widely used to interrogate gene function in whole organisms, and light-activatable derivatives can reveal spatial and temporal differences in gene activity. We describe here a new class of caged morpholino oligonucleotides that can be activated by the bacterial nitroreductase NfsB. We characterize the activation kinetics of these reagents in vitro and demonstrate their efficacy in zebrafish embryos that express NfsB either ubiquitously or in defined cell populations. In combination with transgenic organisms, such enzyme-actuated antisense tools will enable gene silencing in specific cell types, including tissues that are not amenable to optical targeting.
authors: Departments of Chemical and Systems Biology and Developmental Biology, Stanford University School of Medicine , Stanford, California 94305 United States.
authors: Sayumi
authors: S
authors: Yamazoe
authors: Lindsey E
authors: LE
authors: McQuade
authors: James K
authors: JK
authors: Chen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D060326:Chemistry Techniques, Synthetic; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D005260:Female; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D008027:Light; D060172:Morpholinos / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009601:Nitroreductases / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics
chemical_list: D029968:Escherichia coli Proteins; D060172:Morpholinos; C116054:NfsB protein, E coli; D009601:Nitroreductases