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Docket #: S18-496

Control of gene editing and gene expression via integrated anti-CRISPR proteins

Stanford researchers in the Qi Lab have patented methods to control CRISPR-based gene editing and regulation using anti-CRISPR (Acr) proteins. While CRISPR systems offer significant benefits for gene editing and expression in various organisms, they also pose risks due to irreversible outcomes and potential misuse. To address these concerns, the researchers developed methods to safely and reversibly control CRISPR activity, enabling precise tuning. These methods include inhibition of gene editing and inducible control of gene regulation, allowing the design of robust gene circuits in mammalian cells and enabling new genome engineering applications.

Stage of research
The inventors have characterized Acr proteins and shown that a specific Acr is a potent regulator of (d)Cas9 activity in a wide variety of contexts and cell types. Additional development is ongoing.

Applications

  • Research tool:
    • Inhibit CRISPR-mediated gene editing and regulation
    • Tunable control over CRISPR-based gene regulation
    • Construct intricate synthetic circuits within organisms
    • Design pulsatile gene expression to fine-tune expression levels and timing
  • Biological security:
    • Generate cells that are immune to unlicensed gene editing applications
    • Preserve the integrity of yeast cell lines used in the production of sensitive materials such as toxic products or controlled substances
    • Safety net for counteracting CRISPR-based gene drives

Advantages

  • Can prevent undesired CRISPR-based genome editing
  • Allows for more advanced, dynamic, and adaptable control over Cas9 function
  • Tunable inhibitor molecule- useful for probing biology in a wide range of contexts
  • Small size of Acrs allows them to be easily incorporated in a wide range of contexts
  • Remains highly efficient in inhibiting CRISPR activity when fused to other gene products
  • Stable integration allows for permanent prevention of gene editing
  • Potential to use dCas9 and Arcs to build dynamic pre-programed gene regulation circuits
  • Can be engineered for multiple CRISPR system

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