On-Target Genome Editing

Study aimed at children’s diseases could help boost agricultural production

On-Target Genome Editing

A recent study from St. Jude Children’s Research Hospital describes a new method for genome editing that could lead to safer, more targeted strategies for treating life-threatening diseases such as some cancers and blood diseases—with less risk of unwanted mutations.

The method “could help speed the transition of genome editing to clinical use, potentially curing a greater number of patients with what are currently intractable congenital diseases and conditions,” says co-researcher Yanghua He, who recently joined CTAHR’s Dept. of Human Nutrition, Food and Animal Sciences from St. Jude.

Small abnormalities in the DNA in a human genome, whether inherited or acquired, can lead to cancer and other diseases. Gene-editing technologies like CRISPR-Cas9 can repair some of these abnormalities, opening up many far-reaching possibilities for treatment.

However, safer and more specific strategies are necessary to avoid creating accidental mutations through the editing process itself. This is where “CHANGE-seq,” the new procedure created by Yanghua and her colleagues, comes in.

The co-authors developed a new method for identifying regions in the genome where the gene-editing process is more likely to misidentify the intended target site. CHANGE-seq, or “circularization for high-throughput analysis of nuclease genome-wide effects by sequencing,” can therefore help researchers figure out whether sites are “on target”—the appropriate ones to be edited—or “off target”—such that editing them could lead to accidental mutations.

This refinement of the gene-editing process has implications beyond repairing mutated genetic sites. It could also be used to modify characteristics in plant and animal species, potentially creating improved yield, greater nutritional value, or increased tolerance to environmental stresses such as drought.

“CHANGE-seq offers the promise of safely accelerating genetic engineering for animal and plant production to relieve the food shortage problem in the world,” Yanghua says. “I envision a benefit to agricultural development in Hawai’i through better methods for interpreting and predicting the unintended effects of gene editing. I hope this will inspire confidence in the safety of the next generation of promising genome-editing applications.”

Read the full study, “CHANGE-seq reveals genetic and epigenetic effects on CRISPR-Cas9 genome-wide activity.”

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