Novel CRISPR-Cas3 Genetic Editing Holds Potential in Curing Disease

A new gene editing system, called CRISPR-Cas3 has been developed by a group of researchers that that can erase long DNA stretches from sites in the human genome. This is a capability that is not easily accomplished through traditional CRISPR-Cas9 systems. This new approach to genetic editing has the capability to find and erase ectopic viruses such as herpes simplex, hepatitis B, and Epstein-Barr, each poses significant detriments to health. These findings were published in a paper on April 8 in the journal Molecular Cell.

“My lab spent the past ten years figuring out how CRISPR-Cas3 works,” said Ailong Ke, Cornell professor of molecular biology and genetics and a corresponding author of the paper. “I am thrilled that my colleagues and I finally demonstrated its genome editing activity in human cells. Our tools can be made to target these viruses very specifically and then erase them very efficiently. In theory, it could provide a cure for these viral diseases.”

CRISPR-Cas3 also positions researchers to scan the genome and analyze non-coding genetic segments. Though these elements compose 98 percent of the genome, they are yet to be documented well. Non-coding DNA acts as regulators in controlling expression of protein coding genes and have been found to play key roles in determining sex and differentiating cells.

Using this technology, it could be possible to screen for these non-coding elements and erase stretches of genetic material. Once these genetic elements are erased, researchers can analyze the lost functions in organisms to determine the role of this non-coding DNA.

Along Ke in this research was Yan Zhang, assistant professor of biological chemistry at the University of Michigan and corresponding author of the publication. Author authors on the paper were Zhonggan Hou, lab specialist in Zhang’s lab, and Adam Dolan, graduate student in Ke’s lab.

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Further collaboration on the work came from Peter Freddolino, assistant professor of biological chemistry and computational medicine and bioinformatics at the University of Michigan, and Sara Howden, University of Melbourne researcher.

Currently, CRISPR-Cas9 systems use bacterial RNA to guide pairing and recognition of DNA sequences. Once matched, the RNA segment directs CRISPR associated protein Cas9 to that specific portion of DNA. Cas9 then cuts the target DNA in a specific location. CRISPR-Cas3 utilizes this same locating process but erases the DNA continuously for up to 100 kilobases rather than halving it.

The publication of this technology documents Ke and colleague’s successful deletion of sequences of targeted DNA in stem cells from a human embryo and in the HAP1 cell type. Though CRISPR-Cas3 holds the potential to better enhance genome-editing than CRISPR-Cas9, the researchers are attempting to control the length of the deleted DNA segment.

“We can’t quite define the deletion boundaries precisely, and that is a shortcoming when it comes to therapeutics,” Ke explained.

CRISPR-Cas3 has currently been filed for patent by the team through the Center for Technology Licensing. Ke’s funding is derived from the National Institutes of Health (NIH) and Zhang is funded by the NIH and the University of Michigan.

Source: University of Cornell