CRISPRi and CRISPRa Screening

CRISPRi and CRSIPRa Screening

Although CRISPR knockout screening has provided a powerful and precise solution to identify and validate novel drug targets, and to elucidate unknown drug mechanisms, there are some biological studies for which CRISPR knockout screens are not applicable. CRISPRi (interference) and CRISPRa (activation) screening now allow us to broaden the range of possible studies through the capacity to reduce or increase gene expression, rather than completely eliminating gene expression.

These tools provide highly precise and sensitive screening solutions. They can power our customers’ discovery and drug development programs by offering the highest quality and highest confidence in their screening results.

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Learn about CRISPRi and CRISPRa?

Read our blog post about CRISPRi and CRISPRa and their possibilities in functional genomic screening

Forward, Genetics: New Tools In Functional Genomic Screening

Dharmacon/Labroots webinar: CRISPRa tools for transcriptional activation studies

Register now!

CRISPRi Screening Tools

CRIPSRi transcriptional repression
  • Model druggability more closely
  • Study essential genes and genes in amplified loci
  • Target non-protein coding regions (e.g. lncRNA)
  • Validate hits from a KO screen with an orthologous tool
  • Combine with KO or CRISPRa screening for high sensitivity screening

CRISPRa Screening Tools

CRIPSRa transcriptional activation
  • Study gain-of-function effects on a genome-wide scale
  • Explore drug-gene interactions by studying gain-of-function phenotypes
  • Target non-protein coding regions (e.g. lncRNA)
  • Validate loss-of-function effects with a reverse-function orthologous tool
  • Combine with CRISPRi screening for network analysis

CRISPRi/a Screening Platform

CRISPRi and CRISPRa screening platforms are based on Horizon’s highly sophisticated CRISPR KO screening platform, which has been used in over 200 screens to date.

Offering

    • Pooled lentiviral approach
    • Cell line(s) from a pre-optimised cell line list or cell line evaluation prior to the screen
    • Human whole-genome CRISPRi or CRISPRa library or custom designed sub library
    • Custom screen design
    • Next-generation sequencing + bioinformatics analysis + hit nominations
    • Timeline 12-24 weeks

Deliverables

    • A list of genes of which inhibition/activation alters response to the compound of interest
    • A final report containing experimental design, all raw & analysed data and conclusions of the study

To learn more about our platforms watch our recorded webinar on CRISPRi & CRISPRa screening

Power Up! CRISPRi & CRISPRa Tools for Genome-Wide Screening

Whole-genome CRISPRi and CRISPRa resistance screens in melanoma cells

Purpose

Proof of concept studies to identify resistance factors against a BRAF kinase inhibitor Vemurafenib (PLX-4032) in A375 melanoma cells that carry a BRAF V600E mutation.

Methods

    • Whole-genome CRISPRi or CRISPRa sgRNA libraries
    • Pooled-based approach: lentivirus transduction of the library into cells followed by selection
    • Treatment with Vemurafenib
    • Cell pellet collection and sample preparation
    • NGS and data analysis using an adapted MAGeCK workflow
CRIPSRa results

Results

  • Highlighted hits have been previously identified and validated by CRISPR KO screening
  • Top hit MED12 was enriched by over 16,000-fold
  • CRISPRi screening platform showed very high sensitivity
  • Multiple novel hits were also identified

Download the complete application note

CRIPSRa results

Results

  • Highlighted hits have been previously identified and validated by CRISPRa screening (Konermann et al., 2014)
  • Top hit EGFR was enriched by over 16,000-fold
  • CRISPRa screening platform was more sensitive than previously published platforms
  • Multiple novel hits were also identified

Download the complete application note

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