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Publications of the Week

Optimized CRISPR-Mediated Gene Knockin Reveals FOXP3-Independent Maintenance of Human Treg Identity

By August 30, 2021No Comments

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This week we profile a recent publication in Cell Reports from the lab of
Dr. Megan Levings at the BC Children’s Hospital Research Institute.

Can you provide a brief overview of your lab’s current research focus?

Our lab is working to understand the biological properties of regulatory T cells (Tregs) and develop ways to use them as an immunoregulatory cell therapy.

What is the significance of the findings in this publication?

In this paper we developed an optimized method to genome engineer human Tregs in order to remove or introduce genes of interest. We then used this method to knock out FOXP3, a key Treg lineage transcription factor. We were surprised to find that deleting FOXP3 had a relatively minimal effect on various aspects of Treg biology, including patterns of protein expression, DNA methylation and mRNA expression. These data suggest that FOXP3 may have a limited role in maintaining the identity of mature Tregs.

What are the next steps for this research?

The ability to knock out and knock in genes of interest can now be widely used to explore mechanisms of Treg function as well as to engineer desired properties in the context of cellular therapy.

Funding Sources:

The research was funded by CIHR.


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