Alternative miRNA Design for Therapeutic RNAi Applications
Poster Mar 10, 2015
Anja van Brabant Smith, Barb Robertson, Annaleen Vermeulen, Christina Yamada, Angela Reynolds, Anastasia Khvorova, Devin Leake
The utility of RNA interference in therapeutic applications depends on effective delivery of highly potent molecules. While therapeutic applications of RNAi have historically been focused on introduction of siRNA molecules, microRNAs (miRNAs) have emerged as another important arena for therapeutics. miRNAs regulate gene expression through both translational attenuation and message RNA cleavage and have been shown to be important in many biologies including development, differentiation, and disease. Just as the performance of an siRNA molecule in vivo is heavily dependent upon its design, the design of miRNA inhibitors and miRNA mimics must be optimized for in vivo applications. Here we will discuss design considerations for the stability and potency of miRNA mimic molecules. We show that stabilized miRNA mimic molecules lose functionality compared to our standard miRNA mimic molecules due, in part, to the activity of the stabilized passenger strand acting as a miRNA inhibitor. We will discuss how mismatches affect the activity of the stabilized miRNA mimics, perhaps by generating a passenger strand that is less functional as an inhibitor molecule.
Despite the developments in conventional PCR, the complexity of multiplex Real Time PCR is still limited due to the lack of sufficient detection channels. To achieve high-end multiplexing capacity on standard Real Time PCR machines, Anapa Biotech has developed the MeltPlex® technology (see box on right).READ MORE
Genome-wide association studies (GWAS) have identified more than 100 genetic loci associated with type 2 diabetes. The majority of these are located in the intergenic or intragenic regions suggesting that the implicated variants may alter chromatin conformation. This, in turn, is likely to influence the expression of nearby or more remotely located genes to alter beta cell function. At present, however, detailed molecular and functional analyses are still lacking for most of these variants. We recently analysed one of these loci and mapped five causal variants in an islet-specific enhancer cluster within the STARD10 gene locus. Here, we aimed to understand how these causal variants influence b-cell function by alteration of the chromatin structure of enhancer clusterREAD MORE
Early life stress (ELS) is highly associated with development of psychopathology
and mood disorders in adulthood. Genetic studies have identified variation in the gene calcium voltage-gated channel subunit alpha1C (CACNA1C) to increase risk for several psychiatric disorders. This poster assessed the expression of Cacna1c following prepubertal stress.