Scientists have achieved a genetic feat once thought impossible: removing an entire extra human chromosome using gene-editing technology. In a landmark laboratory study published in PNAS Nexus, researchers used CRISPR-Cas9 to delete the additional copy of chromosome 21 that causes Down syndrome. After the edit, human cells grown in the lab showed gene-activity patterns much closer to normal, marking the first time a chromosomal condition has been corrected at its root in this way.Down syndrome, also known as trisomy 21, occurs when a person is born with three copies of chromosome 21 instead of the usual two. That extra chromosome disrupts the behaviour of hundreds of genes simultaneously, affecting brain development, learning ability and physical health. Because the condition involves an entire chromosome rather than a single faulty gene, medicine has never been able to address its underlying cause. This study directly challenges that long-standing barrier.
How the chromosome was removed using gene-editing therapy
The research team, led by scientists including Ryo Hashizume, worked with skin cells and induced pluripotent stem cells derived from people with Down syndrome. Rather than altering individual genes, the scientists designed CRISPR-Cas9 to target the surplus chromosome itself.By exploiting subtle genetic differences between the three chromosome copies, the researchers programmed CRISPR to cut only the extra chromosome 21. Multiple targeted cuts were introduced, and the cell’s DNA-repair response was briefly altered to increase the likelihood that the damaged chromosome would be lost during cell division. The result was what the authors describe as “trisomic rescue”, in which cells reverted from three copies of chromosome 21 to the normal two.“We demonstrated that it is possible to selectively eliminate the extra chromosome while preserving the normal ones,” the researchers wrote in the study.
What changed inside the edited cells
Once the extra chromosome was removed, the cells showed clear biological improvements. Genes that had been overactive due to trisomy returned toward typical activity levels, and several cellular stress signals linked to Down syndrome were reduced. Key pathways involved in development and metabolism also showed signs of recovery.These results suggest that many of the molecular effects of trisomy 21 stem directly from the presence of the extra chromosome and can be reversed when it is removed, at least at the cellular level.Despite its importance, the research does not represent a medical therapy. The experiments were conducted only in cells grown in laboratory conditions, where researchers can tightly control the editing process. Removing an entire chromosome inside a living body would pose major technical and safety challenges.Editing at this scale carries risks, including unintended damage to other parts of the genome or long-term genetic instability. For this reason, the authors emphasise that extensive further research would be required before any consideration of animal studies or human applications.
What the discovery could mean going forward
Even with those limits, the study reshapes how scientists think about chromosomal disorders. It suggests that conditions caused by extra chromosomes are not inherently untouchable and that gene editing could one day address gene-dosage problems rather than individual mutations.In the long term, similar strategies might be explored for other trisomies, such as trisomy 13 or trisomy 18, which often lead to severe disability or early death. These possibilities remain theoretical, but the study provides a foundation for future research.The findings also raise ethical questions. Researchers and disability advocates stress that any future clinical use would require careful dialogue with people with Down syndrome and their families, and thoughtful consideration of how such technologies are framed and applied.For now, the work stands as a scientific milestone rather than a cure. It shows for the first time that an extra human chromosome can be removed using gene editing and that many of its effects can be reversed in laboratory cells. As the authors conclude in PNAS Nexus, the study opens a new research path that could fundamentally change how scientists approach chromosomal conditions while emphasising how much work still lies ahead.