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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)
Recently we have demonstrated that hammerhead ribozymes can be fully substituted with 2'-amino pyrimidines without detriment to the catalytic activity, provided that positions 2.2 and/or 2.1 are not modified. We now report on the potential molecular mechanisms by which 2'-amino groups at these positions inhibit the ribozyme cleavage activity. In the(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)
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)
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)
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)
The uniform 2'-pyrimidine modifications have been found to inhibit ribozyme cleavage activity. However, in the present study we show that a good cleavage activity can be achieved for the 2'-amino modified ribozymes when their sequences were designed to contain only a few pyrimidines in helix I. In particular, ribozymes with no pyrimidines in helix I cleaved(More)
programmed cell death, is a process of active cellular self-destruction that plays a crucial role in cell development and homeostasis. In mammalian cells this process is regulated by a number of gene products. Among them, Bcl-2, Bcl-x L and Mcl-1 inhibit apoptosis, whereas others, such as Bax, Bak and Bad, activate apoptosis (Kroemer, 1997). Dysregulation(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)