University Of Toronto Researchers Mine "Dark Transcriptome" To Create First Potential Drug Molecules From Long Noncoding RNA

University of Toronto engineers synthesize molecules from the "dark transcriptome" to create potent anti-inflammatory drugs from long noncoding RNA.

By: AXL Media

Published: Mar 11, 2026, 5:34 AM EDT

Source: The information in this article was sourced from University of Toronto Faculty of Applied Science & Engineering

Unlocking the Secrets of Noncoding DNA

For decades, the majority of the human genome was considered "junk DNA" because it did not provide the instructions for building proteins. While roughly 25% of our DNA encodes proteins via messenger RNA (mRNA), nearly half of our genetic blueprint produces long noncoding RNA (lncRNA)—strings of RNA that interact with biomolecules but do not create proteins. Professor Omar F. Khan and his team at U of T Engineering have now successfully synthesized these molecules outside of a biological cell, marking the first time the "dark transcriptome" has been utilized as a direct source for drug discovery.

Targeting Chronic Inflammation Through Gene Regulation

The team focused their initial efforts on chronic inflammation, a biological response linked to conditions ranging from sepsis and arthritis to cardiovascular disease. Because lncRNA is believed to play a role in gene regulation—essentially acting as a volume knob for the expression of certain genes—the researchers hypothesized that specific sequences could be used to "shut down" overactive inflammatory responses. According to lead author Janice Pang, the goal was to identify natural sequences that could be modified to promote healing when the body’s innate processes become self-destructive.

Synthesis and Delivery of lncRNA Nanoparticles

The researchers identified three promising lncRNA sequences—GAPLINC, MIST, and DRAIR—previously associated with inflammatory regulation. Using in vitro transcription synthesis and high-performance liquid chromatography, the team created the first lab-made copies of these sequences. To ensure the molecules reached their target, the lab utilized its expertise in nanotechnology to package the lncRNA into specialized nanoparticles. When injected into human cell cultures and mice with inflammatory disease, the molecules effectively decreased the production of specific cytokines, the signaling proteins that trigger inflammation.