Researcher Granted $1.63M by NIH to Set Quality Standards for Gene Editing

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by Margarida Maia, PhD |

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A researcher will use a four-year, $1.63 million grant from the National Institutes of Health (NIH) to help set up a quality control system for CRISPR-based therapies aimed at certain genetic disorders, starting with sickle cell disease (SCD).

The grant was awarded to Kiana Aran, PhD, an associate professor of medical diagnostics and therapeutics who heads the Aran Lab at the Keck Graduate Institute (KGI), in California.

CRISPR is a gene-editing tool that allows scientists to correct disease-causing mutations by making changes to a cell’s DNA sequence with relative ease. It involves the use of an RNA molecule that guides an enzyme protein to a specific point in the DNA sequence of a gene. The enzyme then cuts open the DNA at that point and removes some of its building blocks, leaving open a gap where new building blocks can be added.

The tool is not always as precise as it could be, however.

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“CRISPR-based therapies have been advancing so quickly to combat debilitating diseases such as sickle cell disease, but still, no one fully mastered this new type of therapy yet,” Aran said in a university press release. “It is simply not precise enough as we do not have a lot of insight or control of what CRISPR does step-by-step, and that may result in unwanted editing the wrong places in people’s DNA with unknown clinical outcomes.”

Avoiding unwanted genetic changes should lower the potential risks associated with the use of CRISPR-based therapies. Thus, there have been calls for the development of a quality control system.

“Having tools and assays to characterize and evaluate the quality of genome editing reagents and processes will be very valuable to support confident use of the genome editing technologies,” said Samantha Maragh, who leads the genome editing program at the National Institute of Standards and Technology.

SCD is a genetic condition in which red blood cells acquire an unusual sickle-like shape that makes them stiff and sticky. This abnormal sickle shape is caused by a mutation in HBB, a gene that provides instructions for making a protein called beta-globin.

Beta-globin is a component of hemoglobin, a larger protein responsible for carrying oxygen in red blood cells. The HBB mutation leads to the production of an abnormal version of beta-globin that ends up affecting the shape of hemoglobin and of red blood cells themselves.

Previous research has indicated the potential of CRISPR-based therapies to correct this mutation. The grant will provide the opportunity to develop the tools and assays to increase confidence in CRISPR as a “safe, effective, and predictable” therapeutic tool, according to KGI.

“I believe there are some critical checkpoints that can be developed to improve the editing outcome and to eliminate CRISPR designs and versions that are not appropriate to be used for patients,” Aran said. “And even if you are just researching cell lines, these standards will with time be able to save a lot of otherwise wasted efforts and resources.”

Aran also is the chief scientific officer of Cardea Bio, a biotech company focused on producing chips that translate molecular signals into digital information.

The company has developed a special chip, called the CRISPR-Chip, that lets scientists monitor how CRISPR operates in real time. The chip can identify where gene-editing problems may occur, where there might be a need for optimization, and how to develop quality control standards for using CRISPR.

“Having CRISPR quality control standards and tools that correlate the quality of assay reagents with CRISPR’s performance and the editing outcome will greatly enhance our understanding and expand the safe utilization of CRISPR therapies,” Aran said.