Scientists at the University of New South Wales in Sydney have developed a revolutionary CRISPR technology that can turn genes back on without cutting DNA, potentially offering a safer approach to treating genetic diseases including sickle cell disease. The breakthrough, published in Nature Communications and conducted in collaboration with St. Jude Children's Research Hospital in Memphis, represents a third generation of gene editing known as epigenetic editing.
The new technique targets methyl groups, small chemical markers attached to DNA that act like molecular anchors silencing genes. By using a modified CRISPR system to deliver enzymes that remove these methyl tags, researchers can reactivate dormant genes without altering the underlying DNA sequence. When methyl groups were reapplied in laboratory tests, genes turned off again, providing definitive proof that methylation directly controls gene activity.
Professor Merlin Crossley, the study's lead author, explained the significance of the findings in straightforward terms. He noted that they showed very clearly that if you brush the cobwebs off, the gene comes on. The research settles a long-running scientific debate about whether methylation is a cause or consequence of gene silencing, demonstrating that these chemical tags actively control genetic expression.
The technique holds particular promise for treating sickle cell disease, a painful inherited blood disorder affecting millions worldwide. The proposed treatment would work by reactivating the fetal globin gene, which plays a crucial role in delivering oxygen to a developing fetus. Doctors would extract a patient's blood stem cells, apply epigenetic editing in the laboratory to erase methyl tags from the fetal globin gene, then reinfuse the cells into bone marrow where they would generate healthy red blood cells.
The safety advantages of this approach are substantial compared to earlier CRISPR methods. Professor Crossley emphasized that whenever you cut DNA, there is a risk of cancer, which is a serious concern for gene therapy treating lifelong diseases. By avoiding DNA cuts entirely, the epigenetic editing technique sidesteps these potential pitfalls while still achieving the therapeutic goal of gene reactivation.
Professor Kate Quinlan, a UNSW contributor to the project, expressed enthusiasm about the future of epigenetic editing. She noted that their study shows this approach allows researchers to boost gene expression without modifying the DNA sequence, suggesting that therapies based on this technology are likely to have a reduced risk of unintended negative effects compared to first or second-generation CRISPR techniques.
All experiments so far have been conducted in laboratory settings using human cells. The research team from UNSW and St. Jude now plans to test the approach in animal models while also exploring additional CRISPR-related tools. If successful in clinical trials, the technology could transform treatment options not only for sickle cell disease but for a range of genetic conditions involving improperly silenced or activated genes.