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

Researchers at Stanford have developed methods for controlling CRISPR-based gene editing and gene regulation. CRISPR systems have been developed for gene editing and gene expression regulation in both prokaryotic and eukaryotic organisms. While CRISPR systems have many benefits, they also raise concerns due to the irreversible outcomes created by genome editing and the potential for use for malignant, unethical or illegal purposes. To ease these concerns, means to safely and reversibly control the activity of CRISPR tools are needed. Moreover, such means of control will provide new applications reliant on precisely tuning CRISPR activity. To help meet this need, the inventors have developed methods of using anti-CRISPR (Acr) proteins to stop CRISPR-mediated gene editing and regulation. This includes inhibition of gene editing, as well as inducible control of gene regulation. Moreover, it is possible to design robust gene circuits, such as those with pulse generators, within mammalian cells, thereby enabling novel methods for engineering genomes in a wide range of contexts.

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.