Marianne Leirdal

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In mammalian cells, RNA duplexes of 21-23 nucleotides, known as small interfering RNAs (siRNAs) specifically inhibit gene expression in vitro. Here, we show that systemic delivery of siRNAs can inhibited exogenous and endogenous gene expression in adult mice. Cationic liposome-based intravenous injection in mice of plasmid encoding the green fluorescent(More)
For the therapeutic application of catalytic nucleic acids it is desirable to have small, stable and inexpensive compounds that are active at physiological Mg(2+) concentrations. We have explored the possibility of using the versatile 10-23 DNA catalytic core to suppress the expression of the protein kinase Calpha (PKCalpha) isoform in malignant cells. By(More)
Small interfering RNAs (siRNAs) mediate RNA interference (RNAi), a process in which target mRNAs are degraded. Here, we have investigated the efficacy of preformed siRNAs to modulate the expression of protein kinase Calpha (PKCalpha) and green fluorescent protein (GFP) in mammalian cells. We show that specific inhibition of PKCalpha and GFP can be achieved(More)
Malignant gliomas are refractory to conventional therapies, including surgery, radiotherapy and chemotherapy. Thus, a variety of therapies such as the inhibition of angiogenesis and signal transduction pathways have been attempted. In the present study, we have evaluated the combined effect of endostatin, an inhibitor of angiogenesis, and a DNA enzyme(More)
Although protein kinase C has been shown to be involved in a wide range of biological functions, the precise role of each isoform in a specific cell function remains to be clarified. Here we demonstrate that a ribozyme specific for the human protein kinase Cα (PKCα), a classical PKC isoform, induces cell death in glioma cell lines. This cell death was(More)
Protein kinase C is a family of serine/threonine protein kinases involved in many cellular responses, including cell survival and apoptosis. We have recently found that specific inhibition of the PKCalpha isoform by nucleic acid enzymes induced apoptosis in sensitive cells. Here we show that in PKCalpha DNA enzyme-treated glioma cells the activation of MAP(More)
Although protein kinase C has been shown to be involved in a wide range of biological functions, the precise role of each isoform in a specific cell function remains to be clarified. Here we demonstrate that a ribozyme specific for the human protein kinase C alpha (PKC alpha), a classical PKC isoform, induces cell death in glioma cell lines. This cell death(More)
Recent progress in understanding how gene products interact in the control of cell proliferation has engendered high hopes for the rational design of specific therapeutic strategies. The demonstration that certain RNA and DNA nucleic acids can enzymatically cleave mRNAs has offered the possibility of inactivating abnormal gene expression. In principle, this(More)
In normal cells, signaling pathways are tightly regulated. However, when they are aberrantly activated, certain pathways are capable of causing diseases. In many tumors, the aberrantly activated signaling proteins include members of the epidermal growth factor receptor family, the Ras proteins, protein kinase C isoenzymes, BCR-ABL fusion protein as well as(More)
BACKGROUND Experimental evidence indicates that various intracellular signalling cascades are altered in tumour cells. Among these, the receptor tyrosine kinase ras-ERK signalling pathway was found to be constitutively active in a significant percentage of human tumours; hence, considerable effort has been directed at finding compounds that inhibit its(More)