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09:05
Pooled CRISPR-Based Genetic Screens in Mammalian Cells
Published on: September 4, 2019
22.8K
A Flexible, Pooled CRISPR Library for Drug Development Screens
Maximilian Blanck1, Milka B Budnik-Zawilska1, Steven R Lenger2
1Horizon Discovery, Cambridge, United Kingdom.
The CRISPR Journal
|October 15, 2020
Summary
A new, modular CRISPR screening library improves negative selection screens for drug discovery. This scalable library enhances target identification and validation across the drug development pipeline.
Area of Science:
- Genomics
- Molecular Biology
- Drug Discovery
Background:
- CRISPR screening enables high-throughput gene manipulation analysis.
- Negative selection screening is crucial but challenging in drug discovery.
Purpose of the Study:
- To assess a new modular genome-wide CRISPR library for improved negative selection screening.
- To evaluate its utility throughout the drug development pipeline.
Main Methods:
- Developed a scalable, modular CRISPR library split into three parts.
- Tested the library using a poly(ADP-ribose) polymerase 1 (PARP1) inhibitor to identify sensitizing genes.
- Simulated hit identification and validated findings via orthogonal drug combination cell panel screening.
Main Results:
- The modular library demonstrated improved negative selection screening capabilities.
- Identified genes that sensitize cells to the PARP1 inhibitor.
- Validated hits using high-throughput cell panel screens.
Conclusions:
- A scalable CRISPR knockout screening library offers multiple applications in drug development.
- Initial hit validation is achievable through high-throughput cell panel screens.
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