CRISPR/Cas9 library screening for drug target discovery

@article{Kurata2017CRISPRCas9LS,
  title={CRISPR/Cas9 library screening for drug target discovery},
  author={Morito Kurata and Kouhei Yamamoto and Branden S. Moriarity and Masanobu Kitagawa and David A. Largaespada},
  journal={Journal of Human Genetics},
  year={2017},
  volume={63},
  pages={179-186}
}
CRISPR/Cas9-based tools have rapidly developed in recent years. These include CRISPR-based gene activation (CRISPRa) or inhibition (CRISPRi), for which there are libraries. CRISPR libraries for loss of function have been widely used to identify new biological mechanisms, such as drug resistance and cell survival signals. CRISPRa is highly useful in screening for gain of functions, and CRISPRi is a more powerful tool than RNA interference (RNAi) libraries in screening for loss of functions… 

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References

SHOWING 1-10 OF 49 REFERENCES

High-throughput screening of a CRISPR/Cas9 library for functional genomics in human cells

TLDR
The development of a focused CRISPR/Cas-based (clustered regularly interspaced short palindromic repeats/CRISPR-associated) lentiviral library in human cells and a method of gene identification based on functional screening and high-throughput sequencing analysis are reported.

Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library

TLDR
The results demonstrate the potential for efficient loss-of-function screening using the CRISPR-Cas9 system and identify 27 known and 4 previously unknown genes implicated in these phenotypes.

Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions

TLDR
A CRISPR-based double knockout system that improves the efficiency of combinatorial genetic screening using an effective strategy for cloning and sequencing paired single guide RNA (sgRNA) libraries and a robust statistical scoring method for calculating genetic interactions (GIs) from CRISpr-deleted gene pairs is introduced.

Genetic Screens in Human Cells Using the CRISPR-Cas9 System

TLDR
A pooled, loss-of-function genetic screening approach suitable for both positive and negative selection that uses a genome-scale lentiviral single-guide RNA (sgRNA) library is described and it is shown that sgRNA efficiency is associated with specific sequence motifs, enabling the prediction of more effective sgRNAs.

Genome-Scale CRISPR-Cas9 Knockout Screening in Human Cells

TLDR
This work shows that lentiviral delivery of a genome-scale CRISPR-Cas9 knockout (GeCKO) library targeting 18,080 genes with 64,751 unique guide sequences enables both negative and positive selection screening in human cells, and observes a high level of consistency between independent guide RNAs targeting the same gene and a high rate of hit confirmation.

Compact and highly active next-generation libraries for CRISPR-mediated gene repression and activation

TLDR
A comprehensive algorithm that incorporates chromatin, position, and sequence features to accurately predict highly effective single guide RNAs (sgRNAs) for targeting nuclease-dead Cas9-mediated transcriptional repression (CRISPRi) and activation ( CRISPRa) is built.

Improved vectors and genome-wide libraries for CRISPR screening

TLDR
A Genome-scale CRISPR Knock-Out (GeCKO) library is used to identify loss-of-function mutations conferring vemurafenib resistance in a melanoma model and reveal new mechanisms in diverse biological models.