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Functional Genomics in Pharmaceutical Drug Discovery

  • Chapter
New Approaches to Drug Discovery

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 232))

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.

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Abbreviations

Cas9:

CRISPR-associated nuclease

CCLE:

Cancer cell line encyclopedia

CRISPR/Cas9:

Clustered regularly interspaced short palindromic repeats/Cas9

CRISPRa:

CRISPR activation

CRISPRi:

CRISPR interference

dsRNA:

Double-stranded DNA

DNA:

Deoxyribonucleic acid

esiRNA:

Endoribonuclease-prepared siRNA

FACS:

Fluorescence-activated cell sorting

GoF:

Gain of function

HCS:

High-content screening

LoF:

Loss of function

miRNA:

MicroRNA

NGS:

Next-generation sequencing

NHEJ:

Nonhomologous end join

OTE:

Off-target effect

RISC:

RNA-induced silencing complex

RNAi:

RNA interference

sgRNA:

(Small) guide RNA

shRNA:

Small hairpin RNA

siRNA:

Small interfering RNA

UTR:

Untranslated region

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Acknowledgments

We very much thank Anne Adams for her help with designing the figures.

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Authors and Affiliations

  1. Bayer Pharma AG, Muellerstr. 178, 13353, Berlin, Germany

    Robert Adams, Michael Steckel & Barbara Nicke

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  1. Robert Adams
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  2. Michael Steckel
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  3. Barbara Nicke
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Corresponding author

Correspondence to Barbara Nicke .

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Editors and Affiliations

  1. Drug Discovery-Cross Indication Platform, Bayer Pharma AG, Wuppertal, Germany

    Ulrich Nielsch

  2. Drug Discovery-Cross Indication Platform, Bayer Pharma AG, Berlin, Berlin, Germany

    Ulrike Fuhrmann

  3. Drug Discovery-Global External Innovation & Alliances, Bayer Pharma AG, Berlin, Berlin, Germany

    Stefan Jaroch

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Adams, R., Steckel, M., Nicke, B. (2015). Functional Genomics in Pharmaceutical Drug Discovery. In: Nielsch, U., Fuhrmann, U., Jaroch, S. (eds) New Approaches to Drug Discovery. Handbook of Experimental Pharmacology, vol 232. Springer, Cham. https://doi.org/10.1007/164_2015_27

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