Functional Genomics in Pharmaceutical Drug Discovery

Abstract

Targeted therapies in personalized medicine require the knowledge about the molecular changes within the patient that cause the disease. With the beginning of the new century, a plethora of new technologies became available to detect these changes and use this information as starting point for drug development. Next-generation genome sequencing and sophisticated genome-wide functional genomics' methods have led to a significant increase in the identification of novel drug target candidates and understanding of the relevance of these genomic and molecular changes for the diseases. As functional genomic tool for target identification, high-throughput gene silencing through RNA interference screening has become the established method. RNAi is discussed with its advantages and challenges in this chapter. Furthermore the potential of CRISPR/Cas9, a gene-editing method that has recently been adapted for use as functional screening tool, will be briefly reviewed.

Chemical genetic-based phenotypic screen reveals novel regulators of gluconeogenesis in human primary hepatocytes

“… 4 One challenge of small-molecule library-based phenotypic screening is the difficulty to decipher the targets of effective small molecules, though modern technologies including mRNA, protein, or image-based profiling greatly facilitate and accelerate the deconvolution process. 5 On the other hand, functional genetics approaches (e.g., siRNA and CRISPR) are used to identify potential drug targets, 6 but large amount of effort and time-consuming processes are required to select the appropriate targets and develop specific molecules for those targets.…”