Duke University Engineers Revolutionize CRISPR Technology for Precision Genome Editing

In a groundbreaking development, a team of engineers at Duke University has unveiled a revolutionary method that significantly expands the reach of CRISPR technologies. The original CRISPR system, which could only target 12.5% of the human genome, has now been superseded by this new technique, enabling access to nearly every gene. This breakthrough holds the potential to treat a broader spectrum of diseases through advanced genome engineering.

Published on October 4 in the esteemed journal Nature Communications, the research involved collaborative efforts from renowned institutions such as Harvard University, Massachusetts Institute of Technology, University of Massachusetts Medical School, University of Zurich, and McMaster University.

CRISPR-Cas, originally a bacterial immune system, deploys RNA molecules and CRISPR-associated (Cas) proteins to precisely target and annihilate the DNA of invading viruses. Since its discovery, researchers have been racing to develop a myriad of CRISPR systems for applications in gene therapy and genome engineering.

The key to genome edits lies in Cas proteins, which employ both a guide RNA and a protospacer adjacent motif (PAM) to locate and cut the targeted DNA. The widely used CRISPR-Cas system, Cas9 from Streptococcus pyogenes bacteria (SpCas9), relies on a PAM sequence of two guanine bases (GG) in a row.

Building on previous advancements, the research team, led by Chatterjee, utilized bioinformatics tools to engineer new Cas9 proteins. Notably, Sc++, requiring a single guanine base PAM, expanded the editing potential to nearly 50% of all DNA sequences.

In a collaborative effort, Harvard researchers engineered SpRY, capable of binding to any of the four DNA bases forming the PAM. Merging the strengths of both systems, the researchers introduced a groundbreaking variant, SpRyc, overcoming the limitations of the individual enzymes.

“CRISPR is a great tool for editing specific DNA, but we’re still restricted on which genes we can edit. With this new tool, we can target nearly 100% of the genome with far more precision,” explained Chatterjee.

While SpRyc exhibited a slower cutting pace, it outperformed traditional enzymes in editing specific DNA sections with enhanced accuracy. The team explored the therapeutic potential of SpRyc in treating genetic diseases previously untreatable with standard CRISPR systems, such as Rett syndrome and Huntington’s disease.

“There is a lot of potential with SpRyc, whether it’s exploring how to translate it into the clinic or finding ways to make it even more efficient,” expressed Chatterjee. The team looks forward to unraveling the full capabilities of this groundbreaking CRISPR tool.

Source: Link to the full research article