For decades, scientists puzzled over whether the tiny chemical tags that cling to our DNA were simply genetic clutter or something far more powerful. These tags, called methyl groups, were often dismissed as the cobwebs of the genome and harmless reminders of genes no longer in use.
Now, researchers at UNSW Sydney, working with colleagues at St Jude Children’s Research Hospital in Memphis, have pushed those doubts aside. In a study published in Nature Communications, they show that methyl groups are not just passengers on silenced genes, but the very anchors that keep them switched off. Remove them, and the genes spring back to life.
“We showed very clearly that if you brush the cobwebs off, the gene comes on,” said Professor Merlin Crossley, UNSW’s Deputy Vice-Chancellor Academic Quality. “And when we added the methyl groups back, the gene turned off again. So these aren’t cobwebs — they’re anchors.”
This breakthrough comes thanks to a new wave of CRISPR technology. The third generation of CRISPR, known as epigenetic editing, targets the chemical tags sitting on top of the genome. By removing methyl groups from silenced genes, scientists can lift the brakes without ever touching the underlying DNA sequence.
For people with Sickle Cell disease, where a genetic glitch distorts red blood cells, causing pain, organ damage, and shortened lives, the new approach could be transformative. The new CRISPR method reactivates the fetal globin gene, which naturally supplies oxygen in the womb but shuts down after birth.
“You can think of the fetal globin gene as the training wheels on a kid’s bike,” said Professor Crossley. “We believe we can get them working again in people who need new wheels.”
The process involves collecting a patient’s blood stem cells, using CRISPR to remove the methyl tags blocking the fetal globin gene, and returning the edited cells. Once back in the bone marrow, they generate healthier red blood cells without the risks of cutting into DNA.
The implications extend far beyond one disease. Co-author Professor Kate Quinlan said that many genetic disorders could be treated by turning specific genes on or off through methyl group editing.
“We are excited about the future of epigenetic editing,” she says. “Our study shows that we can boost gene expression without modifying the DNA sequence. That means therapies based on this approach are likely to have fewer unintended side effects.”
So far, the work has been carried out in test tubes with human cells. The next step is testing in animals before progressing to clinical trials. But the bigger picture, said Professor Crossley, is that this technology is only the beginning.
“Perhaps the most important thing is that it’s now possible to target molecules to individual genes,” he says. “We’ve shown we can add or remove methyl groups, but there are other changes we could make to tune gene activity. This is the very beginning of a new age.”