PAUL DIEHL
Cellecta, Inc., 320 Logue Avenue, Mountain View, CA 94043, USA
New genome-wide functional analysis tools needed to accelerate drug development

Abstract

Since the first human genome was sequenced over 10 years ago, a tremendous amount of data has been collected and associated with biological traits, responses, and disease processes. While this information has provided a basis for many new diagnostics, it has not stimulated significant development of novel therapeutics. For new drug development, a more sophisticated understanding of how genes function is required. While there are some techniques that can be used to investigate the function of individual genes, few options exist for genome-wide functional analysis. Only two technologies currently form the basis of techniques for broad-based genetic screens that assess the functions of large numbers of genes in a single assay: RNA interference and CRISPR knockout screens. To make real progress in understanding the disease process and identifying novel therapeutic approaches, new more powerful methods are required.

INTRODUCTION

Despite the need for new innovative therapies to address growing health demands and increasing levels of R&D investment by pharmaceutical companies, the rate of novel drug development has remained level with about 35-40 new approvals each year (Figure 1) (1). Moreover, the approximately 1,500 therapeutic compounds currently approved for general market use all target only about 300 gene products, and many newly developed compounds in trials are also directed toward these same known targets. The potential number of targets for new therapeutics, however, is significantly larger. DrugBank (2) associates over 4,000 targets with the 7,500 compounds in its database. GeneCards (3) catalogues over 10,000 genes that have data indicating they "cause, predispose, or protect from diseases." Granted that all these may not be suitable drug targets, it is clear the current pharmacopeia exploits less than 10 percent of the potentially targetable gene products.

Since the human genome was deciphered about 10 years ago, there has been a tremendous explosion in the studies that associate genes with any number of phenotypes. Researchers have identifie ...