Synthetic Lethality Screens Using RNAi in Combination with CRISPR-based Knockout in Drosophila Cells

Bio-protocol
Benjamin E HousdenNorbert Perrimon

Abstract

A synthetic lethal interaction is a type of genetic interaction where the disruption of either of two genes individually has little effect but their combined disruption is lethal. Knowledge of synthetic lethal interactions can allow for elucidation of network structure and identification of candidate drug targets for human diseases such as cancer. In Drosophila, combinatorial gene disruption has been achieved previously by combining multiple RNAi reagents. Here we describe a protocol for high-throughput combinatorial gene disruption by combining CRISPR and RNAi. This approach previously resulted in the identification of highly reproducible and conserved synthetic lethal interactions (Housden et al., 2015).

References

Aug 20, 2005·Nature Reviews. Cancer·William G Kaelin
Mar 10, 2015·ELife·Bernd FischerMichael Boutros
Sep 3, 2016·Cold Spring Harbor Protocols·Benjamin E HousdenNorbert Perrimon
Sep 3, 2016·Cold Spring Harbor Protocols·Benjamin E Housden, Norbert Perrimon

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Citations

Dec 1, 2017·Proceedings of the National Academy of Sciences of the United States of America·Benjamin E HousdenNorbert Perrimon
Dec 24, 2019·Current Protocols in Molecular Biology·Justin A BoschStephanie E Mohr
Oct 3, 2019·Science Signaling·Hilary E NicholsonWilliam G Kaelin

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