This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Researchers have developed a new approach that uses synthetic DNA molecules to target cancer-linked genes directly, opening new possibilities for future treatments, diagnostics and biological research. The study focuses on a long-standing challenge in genetic medicine: how to accurately target specific sections of DNA inside cells.
While many modern genetic medicines work by targeting RNA, the molecule that carries genetic instructions from DNA, directly targeting DNA itself has proven much more difficult. The research is published in the journal Nucleic Acids Research. David Rusling, an associate professor of bioengineering in the university's School of Medicine, Pharmacy and Biological Sciences, is senior author of the paper and has worked in the field for more than 20 years.
He said the new approach could provide a more precise way of controlling gene activity. "Most drugs target proteins, which are the end product of a long biological process. If you target DNA directly, you're working at the very start of that process.
Each cell contains only two copies of a gene, so in theory it offers a highly efficient way to influence how genes behave." The team used specially designed pieces of synthetic DNA known as triplex-forming oligonucleotides, or TFOs. These molecules are designed to recognize and attach to specific DNA sequences, allowing researchers to target individual genes while leaving the rest of the genome untouched. A major obstacle has been that naturally occurring DNA bases do not bind strongly enough to double-stranded DNA to be effective inside cells.
To overcome this, the researchers incorporated a commercially available synthetic DNA base known as Z. The modification allowed the synthetic DNA molecules to bind more strongly and selectively to difficult-to-target regions of DNA that contain high levels of the genetic building blocks guanine (G) and cytosine (C). These GC-rich regions play important roles in controlling gene activity but have historically been challenging to access.
The researchers tested the approach on MYC, a gene that is known to drive the growth of many cancers when it becomes overactive. The modified DNA molecules successfully attached to the target DNA and reduced MYC gene activity by between 50% and 80% in laboratory experiments. The new molecules outperformed both unmodified DNA and several previously developed approaches that attempt to target the same DNA regions.
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