Skip to content

Discovering PARP inhibitor resistance mechanisms using genome-wide and focused CRISPR screens

In this webinar, Dr. Stephen Pettitt explains how he applies genome-wide targeted mutagenesis screens to elucidate the genetic basis of drug resistance. Using mouse and breast cancer cell lines, Dr. Pettitt’s team developed a targeted, genome-wide mutagenesis screen to identify mutations responsible for resistance to the potent PARP inhibitor talazoparib (BMN 673). The screen yielded one particularly interesting point mutation in the PARP1 gene. This mutation disrupted the ability of PARP1 to bind DNA, demonstrating that DNA binding is necessary for the action of talazoparib. Dr. Pettitt will describe how he then employed a high-density, focused sgRNA library targeting PARP1 to generate further mutants that he used to elucidate details of the structure-function relationships of PARP1. This research is not only important for unravelling the mechanisms underlying drug resistance, but it may improve future treatment plans for cancer patients.

In this tutorial, you will find:

  • How to use genome-wide CRISPR screening for mutant discovery
  • How to create a highly diverse, sgRNA library from Twist Bioscience for targeted, subtle mutations
  • How knowledge of the structure-function relationships of PARP1 mutants can inform treatment of cancer patients with these drugs


Photo of Stephen Pettitt

Stephen Pettitt, PhD

Staff Scientist, Institute of Cancer Research, London UK

Tutorial brought to you by

Twist Bioscience Logo

[Twist Bioscience] Webinar Sept 23 2018 Discovering PARP inhibitor

  • Subscribe to Watch this Premium Tutorial

    Get more information from Twist Bioscience and get instant access.
  • ​​All emails include an unsubscribe link. You may opt-out at any time. See our Privacy Policy & Terms & Conditions
  • This field is for validation purposes and should be left unchanged.

All Bitesize Bio emails contain an unsubscribe link.
You can review our privacy policy, cookie policy and terms and conditions online.

Share this to your network:
Scroll To Top