DURHAM – Applications of the ARCUS® genome editing platform, a proprietary technology from Durham-headquartered Precision BioSciences, were studied in research now published online by Nature Communications. The study demonstrated the technology may be used to edit outside of the nuclear genome.
The paper, “Mitochondrial targeted meganuclease as a platform to eliminate mutant mtDNA in vivo” was led by Carlos T. Moraes, Ph.D., Esther Lichtenstein Professor in Neurology at the University of Miami Miller School of Medicine, with Ugne Zekonyte as first author, reports preclinical results using an ARCUS nuclease to target mitochondrial DNA (mtDNA) and reduce levels of mutant mtDNA in vivo.
“In the past, mitochondrial-targeted nucleases have been successful in shifting mtDNA heteroplasmy but have come with unwanted drawbacks, most notably large size, heterodimeric nature, inability to distinguish single base changes, or low flexibility and effectiveness,” said Dr. Moraes in a statement issued by Precision BioSciences. “In this study, a mitochondrial-targeted ARCUS nuclease (mitoARCUS) used to edit mutant mtDNA was particularly effective, in part because of the nuclease’s small size and single protein nature. We are very excited with this early research and the great promise we believe it suggests for using ARCUS editing in patients with mtDNA diseases in the future.”
ARCUS® uses sequence-specific DNA-cutting enzymes, or nucleases, designed to either insert (knock-in), remove (knock-out), or repair DNA of living cells and organisms, according to the company, and is based on a naturally occurring genome editing enzyme, I-CreI.
Researchers reported mitoARCUS-induced heteroplasmic shifts of up to 60% in vitro, with changes persisting for up to three weeks. The research study involved juvenile and adult mice.
“This is the first time ARCUS has been used to edit outside the nuclear genome and has done so with encouraging safety and efficacy in this mouse model,” said Derek Jantz, Ph.D., co-author of the paper and Chief Scientific Officer at Precision BioSciences in a statement. “We continue to see promising results in preclinical studies suggesting that ARCUS could potentially effectively edit mutant mtDNA in vivo in human clinical trials. I congratulate Carlos and his team on this research and look forward to further work on this program.”
Last week, the company announced the appointment of Alex Kelly to Chief Financial Officer, who had served on an interim basis in that role since December 2020.