Researchers at the University of New South Wales (UNSW) Sydney are developing a revolutionary new approach to tackling genetic diseases. Combined with cutting-edge CRISPR technology, they’re making this innovative new approach possible. This new approach, called epigenetic editing, has the potential to transform treatment for diseases like sickle cell disease. Led by UNSW’s Professor Merlin Crossley, Deputy Vice-Chancellor Academic Quality, the study is the first time that scientists have been able to visualize dynamic regulation done by chemical tags on DNA that affect gene expression without physically cutting DNA strands.
To begin with, CRISPR technology has already evolved tremendously since its original conception. At first, the earliest generation of CRISPR technologies operated based on a simple mechanism to cut DNA sequences and disable malfunctioning genes. This strategy is inspired by watching bacteria that use CRISPR to fight off attacking viruses. They achieve this by cutting the viruses’ DNA sequences. As research developed, the second generation of CRISPR was born, which gave scientists the ability to fix specific letters in the genetic code. Now, with the advent of the third generation, researchers are focusing on epigenetic editing, which examines the surface of genes found in every cell’s nucleus.
The Evolution of CRISPR Technology
CRISPR technology began its terrestrial trailblazing journey after scientists first discovered the technology in the bacteria. There, it served as a robust immunological barricade against viral raids. Through cutting the DNA of invasive organisms, bacteria were able to counteract threats, thus providing the basis for the CRISPR gene-editing mechanism. The first generation did a remarkable job at silencing bad genes. It also brought to light the worries of some scientists that cutting the DNA could have unintended consequences.
The second generation of CRISPR brought a new, more nuanced approach to the table. Now, scientists can hone in on individual bases—the letters that comprise the genetic code—to make highly accurate edits. This breakthrough created unprecedented expectations for the treatment of genetic diseases but was still plagued with issues surrounding safety and precision.
The newest addition to this bloodline is epigenetic editing, noted for its emphasis on regulating genes, rather than changing them. This third generation takes advantage of a naturally occurring process found in cells, RNA interference, to alter gene expression without creating DNA breaks. Now, scientists have developed a method to manipulate these chemical tags—specifically methyl groups—on DNA. This gives them the ability to activate or deactivate genes with more accuracy than ever before.
Mechanisms of Epigenetic Editing
Epigenetic editing depends on our knowledge of these methyl groups. These tiny, dynamic pockets of chemical activity bind to stretches of DNA and control the very conductors of gene expression. For decades, scientists argued over whether these methyl tags were causing gene silencing or were simply markers left over from genes that had switched off. Though a bit stigmatized ourselves, Professor Crossley’s recent field study brought the academic lens into sharper focus on this question.
By demonstrating that removing methyl groups can activate silenced genes, the study highlights the potential therapeutic applications of this technology. To do this, researchers used epigenome editing methods to un-silence the HBG gene. This gene is necessary for hemoglobin production and therefore provides hope for people with sickle cell disease.
The findings of this study were published in the journal Nature Communications and can be referenced with DOI: 10.1038/s41467-025-62177-z. Recently, though, the field has seen exciting progress in understanding how these epigenetic mechanisms might be therapeutically tapped into.
Potential Applications in Treating Genetic Diseases
The impacts of epigenetic editing reach far beyond sickle cell disease. In future medical practices, doctors may collect a patient’s blood stem cells and utilize epigenetic techniques to treat various genetic disorders. Now, with the healthcare professionals to wisely, meticulously modify these methyl groups that control gene expression. This strategy can enable them to sidestep the higher risks associated with more intrusive techniques like DNA editing.
And that’s why therapies that employ epigenetic editing offer a far less dangerous alternative. They will be less prone to unintended off-target consequences than previous iterations of CRISPR technology. These safety attributes stem from the unique power to modulate gene expression. It accomplishes that without actually changing the DNA code itself.
Researchers are just beginning to tap into the vast array of promising applications for epigenetic editing, but the possibilities are nearly endless. This cutting-edge strategy holds the promise of curing multiple genetic disorders by reactivating or silencing specific genes, resulting in improved health with incredible potential.