Researchers at UNSW Sydney have developed a breakthrough form of CRISPR technology that can turn genes back on without cutting DNA, potentially offering a safer approach to gene therapy. The study, published in Nature Communications, settles a long-running scientific debate about how genes are silenced.
Led by Professor Merlin Crossley, UNSW Deputy Vice-Chancellor, and Professor Kate Quinlan, in collaboration with St Jude Children's Research Hospital, the team demonstrated that epigenetic editing—removing chemical tags called methyl groups from DNA—can reactivate silenced genes without altering the underlying genetic sequence.
Settling a Scientific Debate
For years, scientists have debated whether methyl groups on DNA actively silence genes or are merely byproducts of gene inactivity. This study provides definitive evidence that methylation directly controls gene activity. When the researchers removed methyl groups from silenced genes, those genes turned back on. When they added the methyl groups back, the genes switched off again.
"We showed very clearly that if you brush the cobwebs off, the gene comes on," explained Professor Crossley. "And when we added the methyl groups back to the genes, they turned off again."
Safer Gene Therapy
Traditional CRISPR-Cas9 gene editing works by cutting DNA at specific locations—an effective but potentially risky approach. "Whenever you cut DNA, there is a risk of cancer," Crossley noted. "But if we can do gene therapy that does not involve snipping DNA strands, then we avoid these potential pitfalls."
The epigenetic approach could be particularly valuable for treating genetic diseases caused by silenced genes. Rather than trying to insert new genetic material or repair mutations, doctors could simply reactivate the patient's own dormant genes.
Sickle Cell Application
One promising application is sickle cell disease. Current CRISPR treatments for this condition work by reactivating fetal hemoglobin—a gene that naturally turns off after birth. The new epigenetic method could achieve the same result without the risks associated with DNA cutting, potentially making the treatment safer and more accessible.
The findings also have implications for epigenetic reprogramming research in longevity science, where scientists are exploring ways to reset cellular age by modifying epigenetic marks. Understanding precisely how methylation controls gene expression is crucial for developing safe and effective rejuvenation therapies.
