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siRNA Design Principles and Off-Target Effects
Short interfering RNAs (siRNAs) are a major research tool that allows for knock-down of target genes via selective mRNA destruction in almost all eukaryotic organisms. siRNAs typically consist of a synthetic ∼21 nucleotide (nt) RNA-duplex where one strand is designed with perfect complementarity to the target mRNA. Although siRNAs were initially thought to be very target-specific because of their design, it turned out during the last years that all siRNAs have a more or less pronounced intrinsic off-target activity which can make the interpretation of data from siRNA experiments difficult. Here we describe essential ru...
Source: Springer protocols feed by Pharmacology/Toxicology - February 26, 2013 Category: Drugs & Pharmacology Source Type: news

The Design and Structure–Functional Properties of DNA-Based Immunomodulatory Sequences
DNA-based immunomodulatory sequences (DIMS) are promising compounds for the treatment of different diseases, including inflammation and cancer. They act through the interaction with TLR9, a member of the Toll-like receptor family whose essential role in innate immunity was recently recognised by being awarded the Nobel Prize 2011. Combining the data obtained from in vitro and in vivo models with circular dichroism spectroscopy approach, we could show that formation of certain tertiary structures by DIMS can be connected to their specific physiologic effects such as activation of immune cells, induction of interferons and d...
Source: Springer protocols feed by Pharmacology/Toxicology - February 26, 2013 Category: Drugs & Pharmacology Source Type: news

Identification of Aptamers as Specific Binders and Modulators of Cell-Surface Receptor Activity
In recent years, the SELEX (Systematic Evolution of Ligands by EXponential enrichment) technology has established itself as a powerful tool in basic research with promising applications in diagnostics and therapeutics. Oligonucleotides with high-affinities to their targets, denominated as aptamers, are obtained from partially random oligonucleotide pools by reiterative in vitro selection cycles and screening for binding activity. The original technique allowing the identification of aptamers binding to soluble targets, has recently been extended in order to produce aptamers binding to complex targets including receptors an...
Source: Springer protocols feed by Pharmacology/Toxicology - February 26, 2013 Category: Drugs & Pharmacology Source Type: news

The Path to Oncology Drug Target Validation: An Industry Perspective
The advent of a variety of genomic, proteomic and other system-based scientific approaches has raised the expectations of identifying novel targets for oncology drug discovery. However, the complexity of human genome cancer alterations requires a careful analysis of the function of candidate targets identified by these efforts. The postulation and testing of a hypothesis that modulation of a protein or pathway will result in a therapeutic effect in a preclinical setting is crucial for target validation activities. In this chapter, we provide an overview on target identification and validation approaches to interrogate the ...
Source: Springer protocols feed by Pharmacology/Toxicology - February 26, 2013 Category: Drugs & Pharmacology Source Type: news