Showing papers by "Murray J. Cairns published in 2010"
TL;DR: A significant schizophrenia-associated increase in global microRNA expression was associated with an elevation of primary microRNA processing and corresponded with an increase in the microprocessor component DGCR8.
Abstract: MicroRNA expression profiling and quantitative reverse transcription-PCR analysis of the superior temporal gyrus and the dorsolateral prefrontal cortex revealed a significant schizophrenia-associated increase in global microRNA expression. This change was associated with an elevation of primary microRNA processing and corresponded with an increase in the microprocessor component DGCR8. The biological implications for this extensive increase in gene silencing are profound, and were exemplified by members of the miR-15 family and other related microRNA, which were significantly upregulated in both brain regions. This functionally convergent influence is overrepresented in pathways involved in synaptic plasticity and includes many genes and pathways associated with schizophrenia, some of which were substantiated in vitro by reporter gene assay. Given the magnitude of microRNA changes and their wide sphere of influence, this phenomenon could represent an important dimension in the pathogenesis of schizophrenia.
393 citations
TL;DR: It is demonstrated that these miRNAs modulate T cell activation genes in a knock-in and knock-down T cell model and also up-regulated in MS whole blood mRNA, suggesting these mi RNAs or their analogues may provide useful targets for new therapeutic approaches.
Abstract: It is well established that Multiple Sclerosis (MS) is an immune mediated disease. Little is known about what drives the differential control of the immune system in MS patients compared to unaffected individuals. MicroRNAs (miRNAs) are small non-coding nucleic acids that are involved in the control of gene expression. Their potential role in T cell activation and neurodegenerative disease has recently been recognised and they are therefore excellent candidates for further studies in MS. We investigated the transcriptome of currently known miRNAs using miRNA microarray analysis in peripheral blood
229 citations
TL;DR: Nucleic acid-based antiviral agents are versatile, diverse and could complement existing antiviral drugs in combating influenza.
Abstract: Rapid increase in drug-resistant influenza virus isolates, and pandemic threat posed by highly pathogenic avian influenza A and swine flu viruses provide clear and compelling reasons for fast tracking development of novel antiviral drugs. Nucleic acid-based drugs represent a promising class of novel antiviral agents that can be designed to target various seasonal, pandemic and avian influenza viruses. Nucleic acids can be designed to elicit broad-spectrum antiviral responses in the host, by suppressing viral gene expression, or by inducing cleavage or degradation of viral RNA. Immunomodulating nucleic acids, such as double stranded RNA and CpG oligonucleotides, can be potent anti-influenza agents that work by eliciting protective innate and adaptive immunity in the host. By activating the toll-like receptor signaling pathways, these drugs can activate the host's antiviral and inflammatory defenses to combat influenza viruses. Antisense oligonucleotides, small interfering RNAs (siRNA), and nanoRNAs represent sequence specific gene-silencing approaches that could be deployed to suppress or inhibit viral protein gene expression. Lastly, catalytic nucleic acids such as DNAzymes and/or ribozymes can suppress viral replication by repeatedly cleaving viral mRNAs and template RNAs. In summary, nucleic acid-based antiviral agents are versatile, diverse and could complement existing antiviral drugs in combating influenza.
12 citations
TL;DR: Three platinum complexes in which substituted 9-aminoacridine-4-carboxamides were tethered to a platinum(II)diamine moiety showed a decrease in cytotoxicity, as measured by IC(50) values in HeLa cells, when compared with the parent 7-H, 9-NH(2) compound.
10 citations
TL;DR: The development of siRNA therapeutics is surveyed both in terms of the range of virus species targeted and the strategic approaches employed as well as features commonly observed in the field of nucleic acid drug development.
Abstract: The advent of gene silencing siRNA technology has created opportunities to develop therapeutics based on targeting the genomics of the disease state. Amongst the first applications of siRNA technology, antiviral applications have been quickly and extensively exploited allowing emergence of a range of antiviral therapeutic strategies. Patent activity has encompassed a range of the components required to utilize this technology ranging from the identification of susceptible genomic targets through to the development of vector systems to express the siRNA endogenously or the synthesis of stable RNA oligonucleotides for in vivo therapeutics. Indeed the primary focus of research effort in this area has been to overcome the challenge common to all of gene therapeutics - delivery of the oligonucleotide - to the diseased tissues and organs, sites of infection and/or sites of drug action. Here, we survey the development of siRNA therapeutics both in terms of the range of virus species targeted and the strategic approaches employed. Our study illustrates features commonly observed in the field of nucleic acid drug development. While in vitro studies provide a broad range of molecules and molecular targets for potential therapeutics, the field is severely limited in terms of safe, effective means to deliver the potential siRNA therapeutics in vivo, to the intracellular site of action.
5 citations