# University of Portsmouth: Z-modified triplex-forming DNA cuts MYC promoter activity by 50–80%

- Published: 2026-11-05 06:54 UTC
- Section: Life & Health › Biotechnology
- Tags: triplex-forming oligonucleotides, MYC promoter, nucleobase Z, GC-rich DNA targeting, G-C base pair recognition, quadruplex, gene repression, Nucleic Acids Research, University of Portsmouth
- URL: https://realtech.media/news/rt-2286c88e6d1a1de5802e7b46_university_of_portsmouth/

**Triplex-forming oligonucleotides with the synthetic base Z bound GC-rich MYC promoter elements and reduced promoter activity in laboratory experiments, the authors report.**

![University of Portsmouth: Z-modified triplex-forming DNA cuts MYC promoter activity by 50–80%](https://sgzwpqqelzmajkcubgkl.supabase.co/storage/v1/object/public/rt-media/2026/11/f6aa5dd5fa06fb55.jpg)
*Flocci Nivis, Wikimedia Commons, CC BY 4.0*

A team led by Dr David Rusling at the University of Portsmouth has shown that triplex-forming oligonucleotides (TFOs) carrying the synthetic nucleobase Z reduce the activity of the MYC gene promoter by 50–80% in laboratory experiments. The work was published in Nucleic Acids Research in October 2026 [1]. MYC is a gene associated with the growth of many cancers when it is overactive.

## Why GC-rich DNA is hard to target

GC-rich gene regions are difficult to address because of their high duplex stability, repetitive sequences and tendency to form alternative DNA structures [1]. TFOs are programmable molecules that recognise specific DNA sequences. However, natural nucleobases recognise G-C base pairs poorly in a cellular setting, which has limited the use of TFOs [1].

The authors used parallel-binding TFOs with 6-amino-5-nitropyridin-2-one (Z). This base recognises G-C base pairs independently of pH [1]. According to the University of Portsmouth, Z is commercially available, so laboratories do not need to synthesise it themselves.

## Results at the MYC promoter

The researchers chose two structurally distinct regulatory elements in the MYC promoter. Z-modified TFOs formed stable, sequence-selective triplexes on both [1]. Promoter activity fell by 50–80% in episomal reporter assays and at endogenous gene loci [1].

The strongest repression was seen at a GC-rich element that forms a quadruplex and acts as a structural hub for recruiting transcription factors [1]. According to the University, the modified molecules outperformed unmodified DNA and several earlier approaches aimed at the same regions.

The authors state that this is the first demonstration that a nucleobase modification alone allows parallel-binding TFOs to repress an endogenous gene [1]. They describe it as a general strategy for targeting GC-rich regulatory elements by programmable DNA recognition [1].

Rusling said that most drugs act on proteins, whereas targeting DNA works at the start of the process, and that each cell has only two copies of a gene. The University notes that the molecules could also serve as a research tool for temporarily switching off individual genes. It adds that further research is needed before the technology could be used in patients.

## Sources

1. [Nucleic Acids Research](https://doi.org/10.1093/nar/gkag998)
2. [EurekAlert](https://www.eurekalert.org/news-releases/1150276)

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Source: RealTech, realtech.media — https://realtech.media/news/rt-2286c88e6d1a1de5802e7b46_university_of_portsmouth/