Non-coding RNA (ncRNA) plays a crucial role in regulating cellular functions. Without it, gene activity would not be properly regulated and essential processes like cell division, stress responses, proper embryonic development, and immune regulation, would be disrupted. However, when misregulated, ncRNA can be harmful: it can disrupt normal gene activity and contribute to cancer or viral infections by interfering with the body’s natural processes.
Under the supervision of Professor John Pezacki, graduate students Noreen Ahmed, Nadine Ahmed, and Didier Bilodeau set out to create an artificial enzyme—p19-T111BpyAla—capable of cutting specific small ncRNA molecules, including small interfering RNA and microRNA.
Enzymes are proteins that accelerate biochemical reactions without being consumed in the process, a phenomenon known as bio-catalysis. This property allows them to repeatedly target and cleave harmful ncRNA molecules with remarkable efficiency.
“We are introducing new chemistry into biology by engineering proteins to perform functions not seen in nature. Our goal is to ensure this enzyme reaches specific tissues or organs where it’s needed to treat infections or cancer,” said Professor Pezacki.
In their paper, titled , published in Nature Communications, the team describes how they modified a viral protein (p19), which normally binds small RNAs without cutting them, by adding a metal-binding component and incorporating copper.
Using fluorescence techniques, they confirmed that p19-T111BpyAla successfully cleaves RNA. Their results showed that the modified enzyme cuts miRNAs in human cells and reduces levels of miR-122, a molecule required for hepatitis C virus replication. This highlights the enzyme’s potential for treating hepatitis C and other diseases.
Research on engineered enzymes has applications beyond health care. Bio-catalysis holds potential in pharmaceuticals, manufacturing and industrial processes. The Pezacki team, with recent funding from the New Frontiers in Research Fund, is also investigating how these enzymes can degrade plastics, potentially leading to a solution for reducing plastic waste and environmental pollution.
Looking ahead, Professor Pezacki’s research aims to revolutionize therapeutics through innovative protein engineering. The team is exploring a Trojan horse strategy in which proteins that typically support viruses are modified to become detrimental by including a catalytic site that degrades viral components. Professor Pezacki hopes this approach will create new catalysis-based therapies, offering real-world solutions for managing diseases and advancing biotechnology.
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