31 research outputs found
Effects of protein kinase C activators and staurosporine on protein kinase activity, cell survival, and proliferation in Tetrahymena thermophila.
Effects of increasing dietary concentrations of specific structured triacylglycerides on performance and nitrogen and energy metabolism in broiler chickens
Purification and characterisation of cell survival factor 1 (TCSF1) from Tetrahymena thermophila
Optimization of Lipase-Catalyzed Interesterification of Flaxseed Oil and Tricaprylin Using Response Surface Methodology
Establishment of a Predictive In Vitro Assay for Assessment of the Hepatotoxic Potential of Oligonucleotide Drugs
GapmeR cellular internalization by macropinocytosis induces sequence-specific gene silencing in human primary T-cells
Silencing of microRNA families by seed-targeting tiny LNAs
The challenge of understanding the widespread biological roles of animal microRNAs (miRNAs) has prompted the development of genetic and functional genomics technologies for miRNA loss-of-function studies. However, tools for exploring the functions of entire miRNA families are still limited. We developed a method that enables antagonism of miRNA function using seed-targeting 8-mer locked nucleic acid (LNA) oligonucleotides, termed tiny LNAs. Transfection of tiny LNAs into cells resulted in simultaneous inhibition of miRNAs within families sharing the same seed with concomitant upregulation of direct targets. In addition, systemically delivered, unconjugated tiny LNAs showed uptake in many normal tissues and in breast tumors in mice, coinciding with long-term miRNA silencing. Transcriptional and proteomic profiling suggested that tiny LNAs have negligible off-target effects, not significantly altering the output from mRNAs with perfect tiny LNA complementary sites. Considered together, these data support the utility of tiny LNAs in elucidating the functions of miRNA families in vivo. © 2011 Nature America, Inc. All rights reserved