Anna Moreno
Anna Moreno, PhD
Founder & CEO
Navega Therapeutics
Stanley Qi, PhD
Asst Professor
Dept of Bioengineering
Dept of Chemical and Systems Biology
Stanford ChEM-H Institute
Kristen Brennand, PhD
Faculty Member
Yale School of Medicine
Shondra Pruett-Miller
Shondra Pruett-Miller, PhD
Assistant Member,
St. Jude Faculty
Director, Center for Advanced Genome Engineering
Associate Director, Shared Resources, Comprehensive Cancer Center
St. Jude Children’s Research Hospital
Luke Gilbert,
Luke Gilbert, PhD
Assistant Professor
Helen Diller Family Comprehensive Cancer Center
School of Medicine
Dept of Urology
UC San Francisco

CRISPR: New Techniques and Complex Models

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Mechanisms that harness the targeting power of CRISPR but use an inactivated Cas9 (dCas9) to modulate gene function rather than cut DNA are rapidly increasing in popularity. Versions of these dCas9 complexes can interfere with transcription (CRISPRi), activate gene expression (CRISPRa), and more recently, generate heritable, epigenetic changes (CRISPRoff).

These non-cutting CRISPR methods present additional tools to manipulate gene function with subtle yet essential reasons to employ them. They may be used in combination with one another or alongside non-CRISPR-based techniques, e.g., RNAi, to validate results orthogonally. Interrogating gene function with multiple techniques, each using a different cellular process tackles the constant challenge of data reproducibility head-on.

While studying gene function with multiple methods yields more robust science, another approach to boost data confidence is to use the most biologically relevant cellular models for the disease focus. However, using CRISPR to edit, or modulate gene function in these more complex systems, e.g., differentiated iPSCs, primary immune cells, or organoids, poses numerous challenges. The hurdles can seem difficult to overcome, whether it is acquiring enough cells for a specific readout, complex culture conditions, or donor variability. Understanding the critical considerations for working with these cell types and how they differ from immortalized lines will reduce frustration as labs establish these new capabilities.

Event attendees will receive insights on:

  • Clinical and research applications of CRISPR modulation (CRISPRa & CRISPRi) methods
  • Harnessing the flexibility of editing iPSCs for various end-state cell types
  • Validating results of CRISPR screens using orthogonal methods
  • Generating heritable, epigenetic changes using CRISPRoff

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