Scientists in Japan have made a breakthrough using CRISPR technology to remove the extra chromosome responsible for Down syndrome, restoring more typical function to affected cells.
Down syndrome, which occurs in about 1 in 700 births in the United States, is caused by an additional copy of chromosome 21—a condition known as trisomy 21.
This surplus genetic material disrupts normal development, leading to learning challenges, unique physical features, and various health issues. The extra chromosome increases gene activity, causing cells to work harder and altering how genes and proteins function.
Traditional treatments for Down syndrome do not address the root cause—the extra chromosome. However, a research team led by Ryotaro Hashizume at Mie University has demonstrated that CRISPR-Cas9, a powerful gene-editing tool, can be used to precisely target and remove the unwanted chromosome in laboratory-grown cells. By designing CRISPR guides that specifically recognize the extra chromosome, the team was able to cut it out, a process known as allele-specific editing.
After the surplus chromosome was removed, the cells began to behave more like typical cells. Their patterns of gene expression and protein production normalized, and they showed improved survival and growth rates. The corrected cells also produced fewer harmful byproducts, such as reactive oxygen species, indicating better overall cell health and mitochondrial function.
The researchers tested this approach not only on stem cells but also on mature skin cells from individuals with Down syndrome. In both cases, the method successfully eliminated the extra chromosome in a significant number of cells, suggesting the potential for broader applications across different cell types.
Further analysis revealed that removing the extra chromosome boosted the activity of genes involved in brain development, while genes related to metabolism became less active. This shift could help explain how correcting the chromosomal imbalance improves cell function and supports earlier findings about the impact of trisomy 21 on early brain development.
While this technique is still in the experimental stage and not ready for clinical use, it opens up the possibility of one day correcting the underlying genetic cause of Down syndrome in various tissues, including the brain. The team is working to refine the process to ensure that only the extra chromosome is targeted, minimizing the risk of unintended changes to healthy DNA.
Experts caution that much more research is needed before this approach could lead to therapies for people with Down syndrome.
Still, the study marks a significant advance in genome editing, showing that it is possible to remove an entire chromosome rather than just making small genetic tweaks. Future work will focus on improving the safety and efficiency of the method and understanding how these edited cells perform over time.