In the laboratory, DNA molecules reduced MYC activity by 50–80% — News-Medical
Researchers at the University of Portsmouth have developed modified synthetic DNA molecules to directly target cancer-linked genes. In laboratory experiments, these molecules reduced the activity of the MYC gene by 50–80%. MYC can contribute to the growth of many types of cancer when it becomes overactive, News-Medical reports.
Molecules for recognizing DNA regions
The team used triplex-forming oligonucleotides, or TFOs — specially designed fragments of synthetic DNA. They can recognize and bind to specific DNA sequences, making it possible to target individual genes without affecting the rest of the genome.
Directly targeting DNA is more difficult than working with RNA, which is targeted by many modern genetic medicines. Natural DNA bases do not bind strongly enough to double-stranded DNA under conditions inside cells, which had previously limited the use of TFOs.
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Modified Z base
To strengthen binding, the scientists used a commercially available synthetic DNA base known as Z. It enabled TFOs to bind more strongly and selectively to DNA regions with high guanine and cytosine content. Such GC-rich regions play an important role in regulating gene activity but have historically been difficult to target.
According to the researchers, the modified molecules outperformed unmodified DNA and several previously developed approaches targeting the same regions. The study's lead author, Associate Professor of Bioengineering David Rusling, noted that changing the chemical properties of DNA can overcome the limitations of the original triplex-forming oligonucleotide concept.
The authors also view the technology as a research tool: it could make it possible to temporarily switch off individual genes and study the cellular response. According to the researchers, the method could later be adapted to target different genes by changing the synthetic DNA sequence. The article was published in the journal Nucleic Acids Research; further research is needed before the approach can potentially be used in patients.
