Year: 2010
Type: review
Abstract: The discovery of RNA interference (RNAi) generated considerable interest in developing short interfering RNAs (siRNAs) for understanding basic biology and as the active agents in a new variety of therapeutics. Early studies showed that selecting an active siRNA was not as straightforward as simply picking a sequence on the target mRNA and synthesizing the siRNA complementary to that sequence. As interest in applying RNAi has increased, the methods for identifying active siRNA sequences have evolved from focusing on the simplicity of synthesis and purification, to identifying preferred target sequences and secondary structures, to predicting the thermodynamic stability of the siRNA. As more specific details of the RNAi mechanism have been defined, these have been incorporated into more complex siRNA selection algorithms, increasing the reliability of selecting active siRNAs against a single target. Ultimately, design of the best siRNA therapeutics will require design of the siRNA itself, in addition to design of the vehicle and other components necessary for it to function in vivo. In this minireview, we summarize the evolution of siRNA selection techniques with a particular focus on one issue of current importance to the field, how best to identify those siRNA sequences likely to have high activity. Approaches to designing active siRNAs through chemical and structural modifications will also be highlighted. As the understanding of how to control the activity and specificity of siRNAs improves, the potential utility of siRNAs as human therapeutics will concomitantly grow.
Source: FEBS Journal
Institution: Michigan State University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Funders: National Science Foundation, Michigan State University, National Institutes of Health, College of Engineering, Michigan State University, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, Division of Chemical, Bioengineering, Environmental, and Transport Systems
Awards: G172311494, Development of a parallel, array-based transcription factor expression assay, CDI-Type II: Discovery of Biophysical Mechanisms Inducing Signaling and Cytotoxicity: An Experimental Approach Enabled by Cyber Tools, Phenotype-Targeted Inference of Flux-Enzyme Correlations in Adipocyte Metabolism, G316389574, Develop a Dynamic Model that Incoporates Text-mining to Reconstruct Networks, G6490296102, G7615941542, G79308190, Maximizing siRNA Function through Mechanism-based Sequence and Vehicle Design
OpenAlex ID: W1956713893