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It has been a privilege to watch the growth of RNA interference technology over the last ten years. Starting with a mixture of curiosity and chagrin, the field has grown into a substantial enterprise which impacts (and utilizes resources from) virtually every field of biomedical research. Research in RNAi derives from a set of apparently unconnected observations: strange pigment patterns in plants, unexpected failures and successes in antisense and overexpression studies, small regulatory RNAs in bacteria. If there is an underlying and recurring scientific lesson, it has been: “Pursue the unexpected.” Basic and applied research each advance as a consequence of this pursuit; certainly this has been no better illustrated than in the last ten years of RNAi.
The work of hundreds of researchers in different fields that is reported in this book should provide the reader with both solid information (needed for experimental design and evaluation) and a lively and hopeful scientific story (needed to keep us all going through the long haul of scientific research). Our knowledge of the realm of genetic regulation by small RNAs has grown with remarkable speed. Starting in 1981 with a single known example of a modulatory short RNA (regulating copy number of the ColE1 plasmid), small RNAs are now known to regulate genetic activity at virtually every level: DNA and chromosome structure, transcription, RNA structure and stability, translation, and protein stability. Likewise, our ability to experimentally alter cells using this system has advanced at an unprecedented rate.
RNA Interference (RNAi) technology has rapidly become one of the key methods used in functional genomics. RNAi is used to block the expression of genes and create phenotypes that can potentially yield clues about the function of these genes. In the postgenomic era, the elucidation of the physiological function of genes has become the rate-limiting step in the quest to develop 'gene-based drugs' and RNAi could potentially play a pivotal role in the validation of such novel drugs. In this overview, the basic concepts and applications of RNAi biology are discussed. Leading experts from both academia and industry have contributed to this invaluable reference. The volume is forwarded by Andrew Fire, one of the winners of the 2006 Nobel Prize for the discovery of RNA Interference.
RNA interference is a powerful tool that has been used to inhibit gene function either by increasing the destruction of mRNA corresponding to the gene, or in some cases, by inhibiting the transcription of the gene or the translation of mRNA to the corresponding protein. Exploring gene function by the classical approach of generating mutants of a gene often is much more laborious and time consuming then silencing gene function by RNAi using double-stranded RNA or double-stranded oligoribonucleotides about twenty two nucleotide residues in length. This book edited by Krishnarao Appasani is a timely and comprehensive compendium of information on RNAi and will be useful to experts on RNAi as well as investigators in many fields of research who may be interested in using RNAi to explore problems they are studying.
The RNAi field is only six years old. Research on RNAi has been expanding at an extraordinarily rapid rate, yet the field is in its infancy. There is great interest in using RNAi as a means of exploring gene function during embryonic development and in the adult in many organisms. Many aspects of RNAi remain to be explored. For example, the reactions and the molecules required for RNAi targeted destruction of mRNA are incompletely known. Similarly, the mechanisms of RNAi targeted modification of DNA, which regulates, transcription of DNA, as well as RNA targeted inhibition of mRNA translation are only partially known. Also, the functions of most micro RNA genes have not yet been explored.