Prof. Ouellet Co-Authors Study Advancing DNA Enzyme Design

Jonathan Ouellet, Ph.D., associate professor in the Department of Chemistry and Physics, co-authored a new study published in the Journal of Nucleic Acids that refines the understanding of how synthetic DNA enzymes target and cleave genetic material.

The article, "A Base Pair Outside the Catalytic Core of the I-R3 DNA Enzyme Has a Significant Effect on Its Cleavage Activity: An Improved Catalytic Core Model and an Automated Design Program," introduces a software tool that improves predictions of enzyme activity by accounting for a previously overlooked nucleotide base pair adjacent to the enzyme's catalytic core.

The findings could help researchers design more accurate and efficient DNA enzymes to detect or disrupt viral genetic material. Because these enzymes can be custom-built to recognize specific sequences in single-stranded DNA, they hold promise as diagnostic tools or targeted therapeutics-especially in addressing fast-evolving viral infections.

"Understanding and optimizing DNA enzymes could lead to precise interventions against single-stranded DNA viruses," said Ouelett.

Ouelett cites the highly contagious canine parvovirus (CPV) as a possibility for practical deployment of the tool. "It's very, very infectious. The treatment is usually euthanasia so that it does not propagate to other dogs."

He hypothesizes that enzymes like I-R3 could provide a treatment for dogs infected with CPV. "Cutting the viral DNA in half would inactivate it: no more virus!"

The study was conducted in collaboration with researchers from Concordia University's Department of Biology and Center for Applied Synthetic Biology in Montreal and Dalhousie University's Faculty of Computer Science in Halifax. The IR3 software developed by the team is publicly available at github.com.