Inside a laboratory at the University of Stirling, researchers used a specially designed piece of synthetic DNA to cut activity in the cancer-linked MYC gene by as much as 80 percent. The result, achieved in lab experiments, revives an idea that scientists have pursued for decades: targeting DNA itself to control a gene.
Many genetic medicines act on RNA, the molecule that carries instructions from DNA. Reaching DNA directly has been harder, even though DNA is where those instructions begin. Dr. David Rusling, an associate professor of bioengineering at the University of Stirling’s School of Medicine, Pharmacy and Biological Sciences, has worked on DNA targeting for more than 20 years. He says acting at this early point could offer a precise way to influence gene activity. Each cell holds only two copies of a gene, he notes, though turning that idea into a treatment remains a challenge.
The team’s method uses short, custom-designed synthetic DNA molecules called triplex-forming oligonucleotides, or TFOs. They are built to recognize a chosen DNA sequence and attach to it, rather than bind broadly across the genome. But ordinary DNA building blocks often do not attach strongly enough to double-stranded DNA under conditions inside cells.
To improve the binding, the researchers added a commercially available synthetic DNA base known as Z. The change helped the molecules bind more strongly and selectively to GC-rich DNA regions—stretches containing many guanine and cytosine building blocks. These regions help control gene activity, but have been difficult to target. In tests aimed at MYC, a gene that can drive the growth of many cancers when too active, the modified molecules lowered gene activity by 50 to 80 percent. They also performed better than unmodified DNA and several earlier methods aimed at the same regions.
The findings were published in Nucleic Acids Research in 2026. The study’s authors include Ruolin Ma, and its title describes sequence-specific targeting of GC-rich gene sites using modified TFOs. Rusling said the team is changing the chemistry behind the approach, rather than giving up on the original idea. Earlier versions could recognize DNA precisely in test tubes, but struggled to reach many important sequences in conditions closer to those inside cells.
Access may help the work spread. Some specialized DNA changes have required custom chemistry and expert makers. The Z base used here is commercially available, making it easier for other laboratories to try the approach. Researchers could use the molecules not only to explore future therapies, but also as a temporary way to switch off one gene at a time and observe how cells respond. That could help scientists study cancer and genetic disorders.
The results are still from laboratory experiments, and more research is needed before the method could be tested as a treatment in patients. The approach may be adaptable to other genes by changing the sequence of the synthetic DNA, but that possibility has yet to be demonstrated. For now, the study offers a practical new way to probe difficult DNA regions—and brings a long-standing strategy a step closer to useful research and, potentially, future medicine.