RNA Interference Technology: From Basic Science to Drug Development

by Edited by Krishnarao Appasani , Foreword by Andrew Fire , Marshall Nirenberg

• ISBN13: 9780521205177
• ISBN10: 0521205174
• Edition: Revised
• Format: Paperback
• Copyright: 2011-08-11
• Publisher: Cambridge University Press

Summary

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 2005 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.

Table of Contents

Basic RNAi, siRNA and Gene Silencing Mechanisms

RNAi beginnings: overview of the pathway in C. elegans

Dicer in RNAi: its roles in vivo and utility in vitro

Genes required for RNAi

MicroRNAs: a small contribution from worms

miRNAs in the brain and the application of RNAi to neurons;

Design and Synthesis of siRNAs

Design and synthesis of small interfering RNA (siRNA)

Automated design and high throughput synthesis of siRNA

Rational design of siRNAs with the Sfold software

Enzymatic production of siRNAS;

Vector Development and In Vivo, In Vitro and In Ovo Delivery Methods

Six methods of inducing RNAi in mammalian cells

Viral delivery of siRNA

siRNA delivery by lentiviral vectors: design and applications

Liposomal delivery of siRNAs in mice

Chemical modifications to achieve increased stability and sensitive detection of siRNA

RNAi in postimplantation mouse embryos

In ovo RNAi opens new possibilities for functional genomics in vertebrates;

Gene Silencing in Model Organisms

Practical applications of RNAi in C. elegans

Inducible RNAi as a forward genetic tool in Trypanosoma brucei

RNAi gene silencing in yeast

RNA silencing in filamentous fungi: Mucor circinelloides as a model organism

RNAi and gene silencing phenomenon mediated by viral suppressors in plants;

Drug Target Validation

Delivering siRNA in vivo for functional genomics and novel therapeutics

The role of RNAi in drug target validation: application to Hepatitis C

RNAi in the drug discovery process

RNAi: use in the drug discovery process;

Therapeutic and Drug Development

RNAi-mediated silencing of viral gene expression and replication

RNAi in drug development: practical considerations

RNAi for the treatment of liver diseases

RNAi applications in animal systems;

Genome Wide RNAi and High Through-Put Analysis

High through-put RNAi-by-soaking in Caenorhabditis elegans

Tools for integrative genomics: genome-Wide RNAi and expression profiling in Drosophila

Microarray analysis and RNA silencing to determine genes functionally important in Mesothelioma

High through-put RNAi

Generation of highly specific vector-based shRNAi libraries directed against the entire human genome

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