RNA interference: a chemist's perspective

Since the first unequivocal description of RNA interference (RNAi) in 1998, it has remained one of the hottest topics under investigation, culminating in the award of a Nobel Prize to its discoverers in 2006. Excitement over this technique derives from the ease with which it can be used to switch-of...

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Bibliographic Details
Published inChemical Society reviews Vol. 39; no. 11; pp. 4169 - 4184
Main Authors Gaynor, James W, Campbell, Barry J, Cosstick, Richard
Format Journal Article
LanguageEnglish
Published England 19.10.2010
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Summary:Since the first unequivocal description of RNA interference (RNAi) in 1998, it has remained one of the hottest topics under investigation, culminating in the award of a Nobel Prize to its discoverers in 2006. Excitement over this technique derives from the ease with which it can be used to switch-off a specific gene in almost any organism, thereby allowing the role of that gene to be identified. More importantly, it offers the potential to treat certain diseases by switching-off the causative genes. Key to the RNAi pathway are the small-interfering RNAs (siRNAs), which at 21-23 nucleotides in length are very amenable to analogue development by chemists. However in comparison to the use of oligonucleotides as antisense agents, an area where many chemists first developed an interest in nucleic acids, the RNAi pathway is exceedingly complex. The literature is also complicated by the fact that the phenomenon has been studied in a wide range of organisms. In this tutorial review we have presented the subject from a more chemical perspective, incorporating a glossary to give a clear explanation of the specialist terms. However, the coverage of the biology remains sufficiently detailed to give the reader the necessary insight that we believe will be essential for the successful design of chemically modified siRNA. Covering all the bases of RNA interference: discovery, mechanism, molecular biology, therapeutic potential, siRNA structure and delivery.
Bibliography:James W. Gaynor received his MChem degree from the University of Oxford (Oriel College) in 2004. He moved to the University of Liverpool and under the supervision of Rick Cosstick completed his PhD in Bio-Organic Chemistry in 2008. He continued within the same laboratory as an EPSRC-funded postdoctoral research associate until April 2010 and his research was focussed on various aspects of nucleic acid chemistry, with an interest in its application in biology. He is now a University Teacher in the Liverpool Chemistry Department.
Rick Cosstick studied Chemistry at the University of Birmingham and completed a PhD at the same institution in 1982, under the direction of Professor Stan Jones. After working as a research associate with Professor Fritz Eckstein at the Max Planck Institute for Experimental Medicine, Göttingen, Germany, he joined the Chemistry Department at the University of Liverpool in 1984. He was a visiting Fullbright Scholar at The University of Boulder, Colorado, USA, in 1994. His research interests are in nucleic acid chemistry and he is the author of over 100 refereed papers and book chapters.
Barry J. Campbell studied Zoology at UCNW Bangor before completing a PhD in physiology in 1991 at the University of Liverpool, under Professor Graham Dockray FRS. Research associate and Lectureship posts in both Medicine and Physiology at Liverpool developed expertise in intestinal mucus biology, epithelial glycobiology and bacteria-host cell interaction. A Reader in Clinical Sciences (and a faculty member of the Liverpool NIHR Specialist Biomedical Research Centre in Microbial diseases), his current research examines adherent, invasive E. coli (AIEC)-mucosa interactions in both Crohn's disease and colorectal cancer, where new RNAi technology is being utilised to examine bacteria-activated host cell signal pathways.
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ISSN:0306-0012
1460-4744
1460-4744
DOI:10.1039/b920362c