Beyond the Genome: A Drug for Every Gene?

Abstract

Genomics is revolutionizing the way in which we think about biology. Downstream technologies such as proteomics and structural biology now underpin our understanding of biological structure and function, while genome-wide transcriptome and proteome analysis allow us to gain an impression of the dynamic processes underlying biochemistry and physiology. Nowhere is the impact of genomics greater than in drug discovery. Genomics is now influencing the evolution of the pharmaceutical industry. This presentation will focus on emerging technologies in genomics-based drug design and chemoinformatics as solutions for new lead discovery, the starting point of drug development. It will highlight some of the opportunities and challenges in industrializing the drug design process, and will address the emerging bottlenecks in reducing the design process to genome-wide application. The Importance of Genome-Wide Informatics in Target DiscoveryThe development of computational bioinformatics has been crucial to our understanding of the inter-relationships between specific therapeutic targets and the functional gene families to which they belong. The most comprehensive example of this has undoubtedly been the task of sequencing and assembling the human genome[1,2], a feat that lay at the very edge of our ability to handle such complex computational tasks. Assigning function to the individual genes within the genome is a continuing challenge.The information produced from both public and private genome programs already provides a powerful foundation for future exploitation of genes as targets in drug discovery [3] and comprehensive mining of the human genome for therapeutic targets has uncovered a wealth of new opportunities for exploitation in molecular pharmacology and mechanism-based drug discovery [4]. Traditional High-Throughput Screening Approaches for Lead DiscoveryUntil recently, the contribution made by genomics to drug discovery centred primarily on the production of protein targets for biochemical screening. With bioinformatics allowing the definition of specific therapeutically relevant genes and gene families, many targets have been reduced to discovery practice through high-throughput screening approaches.