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.
Psychiatric Risk Gene Cacna1c and Early Life Stress: Potential Gene-Environment interactions?Poster
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.
A new method for generating arrayed RNAi screening tools for any organismPoster
RNA interference (RNAi) using small interfering RNAs (siRNAs) is an important technology for down-regulation of gene expression and a powerful tool to study cellular processes and pathways. Previously, large collections of siRNAs were available only for traditional experimental model systems, such as human and mouse, and predominantly provided as chemically synthesized libraries.READ MORE
Nitrogen metabolism in Mycobacterium tuberculosis: a systems-based approachPoster
Previous studies suggested that Mycobacterium tuberculosis obtains nitrogen from a diverse range of intracellular nutrients including amino acids. Here, we use a novel system’s based three-pronged approach to define pathways for uptake and assimilation of nitrogen.READ MORE