Chromosomes play a vital role in the body’s physical structure, development and various cellular functions. Human cells normally carry 23 pairs, or 46 chromosomes in total, with two chromosomes in each pair. In some cases, however, there are three copies of chromosome 21 instead of two. This extra chromosome is known, in biological terms, as Trisomy 21, which is considered the primary genetic cause of Down syndrome in medical science.
Down syndrome occurs in roughly one in every 700 people worldwide. It is a chromosomal genetic condition, resulting in certain physical characteristics and individual variation in learning pace, language and other areas of development. People with Down syndrome are sometimes referred to using derogatory terms, which is disrespectful and wrong. With appropriate treatment, education, therapy, rehabilitation and social support, they can lead active and meaningful lives.
While treatment and management of various health and developmental issues associated with Down syndrome are now possible, no established treatment has yet been found to remove the extra copy of chromosome 21 itself. A team of Japanese researchers has now signalled new possibilities regarding this extra chromosome.
Led by Dr Ryotaro Hashizume of Mie University Graduate School of Medicine in Japan, the researchers used CRISPR-Cas9 gene-editing technology to try to remove the extra copy of chromosome 21 from cells with Down syndrome. The study was published on February 18, 2025, in the journal PNAS Nexus. CRISPR-Cas9 is generally used to make targeted changes to a specific part of DNA. But in this study, the goal was much bigger than altering a single gene — it was to remove an entire extra chromosome from the cell.
To identify and target one specific copy among the three chromosome 21 copies, the researchers used an allele-specific CRISPR-Cas9 method. In other words, they precisely targeted whichever of the three chromosomes was the extra one, creating cuts at multiple points on it. This created an opportunity for the targeted extra chromosome to be lost during cell division — a process the researchers described as “trisomic rescue.” The technique was tested on induced pluripotent stem cells (iPSCs) and skin fibroblast cells derived from people with Down syndrome.
In one experiment, after applying CRISPR, 15 out of 40 analysed cells showed the normal count of 46 chromosomes — meaning 37.5 percent of cells in that experiment achieved a “disomy 21” state, with the extra copy of chromosome 21 removed. Further analysis found that, among 72 clones created through the specific CRISPR method, 22 showed disomy 21, or around 30.6 percent. Beyond simply reducing chromosome count, evidence emerged that corrected cells’ gene expression patterns, growth rate and antioxidant capacity also began returning toward normal cell characteristics, with some cellular traits improving alongside the normalised chromosome count.
Another notable aspect of the study is that the researchers did not work only with iPSCs. The technique was also tested on differentiated cells such as fibroblasts, and evidence of extra-chromosome removal was found even in non-dividing cells. This opens up the possibility of future research applying the technique across different cell types.
Though the results are promising, this is not yet a treatment or complete cure for Down syndrome, since the entire study was conducted on isolated human cells in a laboratory setting. CRISPR has not been applied in the body of any person with Down syndrome to remove the extra chromosome 21, so whether the same result would occur in the human body remains unknown. Another major challenge is safety — creating CRISPR cuts at multiple points on an entire chromosome cannot, in every situation, be guaranteed to affect only the targeted chromosome. The study itself found that some genetic changes can occur in the remaining chromosomes. Understanding and controlling the risk of these unintended changes will therefore be essential before any application in humans.
This method of directly targeting the extra chromosome in Down syndrome has opened up an important direction for future research. According to the researchers, the allele-specific method could, in the future, form the basis for more advanced treatment approaches targeting Trisomy 21. Medical scientists say this success in targeting and removing an extra chromosome from within the cell has opened new questions and possibilities not only for Down syndrome research, but for future research into potential treatments for various chromosomal disorders.
Written by the Department of Speech and Language Therapy, Mymensingh College of Physiotherapy and Health Sciences.