Editors: Ralph A. Tripp, Jon M. Karpilow

Frontiers in RNAi

Volume 1

Personal Book: US $0 Special Offer (PDF + Printed Copy): US $153
Printed Copy: US $119
Library Book: US $0
ISSN: 2589-2932
eISSN: 2352-8400 (Online)
ISBN: 978-1-60805-941-6
eISBN: 978-1-60805-940-9 (Online)
Year of Publication: 2014
DOI: 10.2174/97816080594091140101

Introduction

RNA Interference (RNAi) arrived in the scientific community just over a decade ago, and has since blossomed with new connections being made between post-transcriptional gene regulation and such topics as innate immunity, epigenetics, and genome organization. Simultaneously, RNAi “the tool” has facilitated research in countless areas, expanding our understanding of cancer, virology, and stem cell biology while challenging the reliability of in vitro systems to accurately model normal and disease physiology. The contributions of RNAi are expected to grow over the next decade in part due to the current ability to map the host-pathogen interface using RNAi to identify previously unknown interactions. Continued studies of lncRNAs and miRNAs, particularly as they are associated with target identification, are expected to expand our understanding of non-coding RNAs and lead to a more integrated and comprehensive theory of gene modulation. RNAi is currently being used to enhance bioproduction platforms and bioprocessing, a feature that will change the paradigm of biotechnology and drive economic growth in such fields as vaccine development, biofuel production, and industrial manufacturing. There is currently a keen need for expert literature that details recent advances and applications of RNAi technology. The publication being proposed herein will draw upon the expertise of the RNAi Global Initiative (RGI), a worldwide academic-industrial consortium comprised of over fifty universities, all focused on high-throughput genome-wide RNAi screening. With expertise in cancer biology, bioinformatics, host-pathogen biology, bioproduction, as well as RNA biology and chemistry, RGI, together with additional colleagues in academics, government, and industry, is well positioned to provide up-to-date perspectives on the advances and challenges facing the scientific community.

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!

Devin Leake
Vice President of Research and Development
Gen9 Inc.
Cambridge, MA
USA

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