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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We very much thank Anne Adams for her help with designing the figures.
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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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DOI: https://doi.org/10.1007/164_2015_27
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