Science 3 min read

Harnessing Class 1 CRISPR Systems to Improve Human Gene Editing

Image courtesy of Shutterstock

Image courtesy of Shutterstock

Duke University researchers harnessed the less-explored Class 1 CRISPR systems to enhance current human gene-editing techniques.

In a recent paper published in the journal Nature Biotechnology, researchers at Duke University described how  Class 1 CRISPR systems could improve human gene editing.

Aside from turning target genes on and off, the biomedical engineers were able to edit the epigenome in human cells for the first time.

CRISPR-Cas is a defense system which involves bacteria using CRISPR-associated (Cas) proteins and RNA molecules to target and destroy the DNA of invading viruses. The discovery of this phenomenon at Osaka University in 1987 would set a genome-editing revolution in motion.

Researchers soon learned how to repurpose this tool for targeting and editing DNA in human cells. This led to CRISPR-Cas9, which is not only the most commonly used gene-editing tool today but also a Class 2 CRISPR system.

While you’ll find very few bacterias with Class 2 systems, it has a significant advantage over the Class 1 counterparts. Since the Class 2 systems rely on Cas protein to target and cleave DNA, they are theoretically easy to work with.

The Class 1 systems, on the other hand, rely on multiple proteins working together in a complex to target DNA. Researchers call this complex CRISPR-associated complex for antiviral defense or Cascade for short.

Cascade has a remarkably modular structure which allows for a variety of site to attach repressors and activators. As a result of this flexibility, the cascade is an excellent tool for altering gene expression in human cells.

Here is why.

Demonstrating the Capabilities of Class 1 CRISPR Systems

For this part of the study, the researchers attached gene activators to specific sites along with a type I E. coli Cascade complex. Then, they targeted the systems to bind gene promoters, which are responsible for regulating gene expression levels.

Since the experiment did not include the Cas3 protein, Cascade did not cut the DNA or change the underlying DNA sequence. Instead, the researchers demonstrated that the Cascade activator could bind to the correct site and increase the levels of the target gene.

What’s more, it performs this task with an accuracy and specificity that’s worthy of CRISPR/Cas9 – even when the researcher swapped the activator domain for a repressor.

In a statement, the Rooney Family Associate Professor of Biomedical Engineering at Duke, Charles Gersbach said:

“If you were to look at the individual CRISPR systems of all the bacteria in the world, nearly 90 percent are Class 1 systems. CRISPR-Cas biology is an incredible source for biotechnology tools, but until recently, everyone has only been looking at a small slice of the pie.”

After demonstrating the similarities between class 1 and the class 2 CRISPR systems, the researchers are considering other topics. For example, they want to know the difference between these systems and if such contrast has biotechnology applications.

The researchers also intend to use Class 1 systems to address some known issues in CRISPR-Cas research. Example of such includes immune responses to Cas proteins.

Read More: CRISPR Used to Make Programmable Smart Biomaterials

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Sumbo Bello

Sumbo Bello is a creative writer who enjoys creating data-driven content for news sites. In his spare time, he plays basketball and listens to Coldplay.

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