Applications of mass spectrometry to the study of siRNA

RNA interference (RNAi) has quickly become a well‐established laboratory tool for regulating gene expression and is currently being explored for its therapeutic potential. The design and use of double‐stranded RNA oligonucleotides as therapeutics to trigger the RNAi mechanism and a greater effort to understand the RNAi pathway itself is driving the development of analytical techniques that can characterize these oligonucleotides. Electrospray (ESI) and MALDI have been used routinely to analyze oligonucleotides and their ability to provide mass and sequence information has made them ideal for this application. Reviewed here is the work done to date on the use of ESI and MALDI for the study of RNAi oligonucleotides as well as the strategies and issues associated with siRNA analysis by mass spectrometry. While there is not a large body of literature on the specific application of mass spectrometry to RNAi, the work done in this area is a good demonstration of the range of experiments that can be conducted and the value that ESI and MALDI can provide to the RNAi field. © 2010 Wiley Periodicals, Inc., Mass Spec Rev 30:979–998, 2011