Foreword

Great technologies follow similar roads to maturity. A breakthrough discovery leads to rapid early adoption which (more often than not) precedes the identification of limitations. Eventually, solutions are identified and the technology, with all its strengths and weaknesses, is put to the test through wide-spread implementation. This process of maturation takes years and in this regard, RNA Interference (RNAi) is no different than yeast two-hybrid, chip-based gene expression profiling, and monoclonal antibodies.

Once the scientific community overcame the sense of excitement associated with the discovery of non-coding RNA-based posttranscriptional gene regulation, early adopters between 2000-2005 immediately gained insights into the technology’s limitations. Not all siRNAs silenced with equal efficiency. Some siRNA designs activated the innate immune response. Other siRNAs exhibited off-target effects and could induce false positive phenotypes. To some, these challenges might have appeared overly daunting, but given the potential of RNAi, researchers in both academic and industrial settings pressed to find solutions. Algorithms were designed to address issues associated with functionality and position specific chemical modifications were adopted to minimize offtarget effects and activation of the innate immune system. Self-delivering siRNA were developed to address the need to deliver reagents to cell lines that were refractory to lipid-mediated delivery and viral-based gene silencing was constructed to facilitate experiments in systems that required extended periods of knockdown.

While challenges still persist (e.g., therapeutic delivery), overcoming the first wave of technical hurdles has been paramount to expansion of RNAi into new fields of interest. As evidenced in this ebook, continued mechanistic studies are now combined with a host of new developments where RNAi technology is being merged with miniaturized screening platforms, field-specific database infrastructures, host-pathogen interaction mapping, and new (3D) tissue culture models. At the same time, the technology is reaching into more applied fields. RNAi screening is slowly becoming a module of synthetic biology and cell line engineering, and a key component of therapeutic drug repurposing. This expansion of the technology mirrors the growth and development observed with other platforms (e.g., NG Sequencing, PCR) and is indicative that over the course of little more than a decade, RNAi has grown up!