Deleting Extra Chromosomes

Just last week, scientists at Harvard Medical School made significant progress in trying to silence the 21st chromosome in Down Syndrome [1]. Down Syndrome is caused by a failure in the XIST gene, which is supposed to cut out extra chromosomes during development [1]. Cas9 is usually used to fix one specific gene within one chromosome, but to properly fix Down Syndrome, the scientists had to modify the Cas9 protein in such a way that it would silence an entire chromosome, without impacting any of the other chromosomes or disrupting vital cell functions [1]. 

Specifically, they took an enzyme from a bacteriophage that leaves overhangs at the 5-prime and 3-prime ends of DNA, fused it with Cas9, then put the modified Cas9 into a plasmid to make the Cas9 more effective [2]. Then, a single-guide DNA (sgDNA) was used to guide the plasmid to the XIST gene to activate it and silence the entire 21st chromosome [2]. 

They introduced this modified CRISPR technology to human stem cells in a petri dish that had an extra Chromosome 21, and found that it correctly inserted and activated the XIST gene to silence the extra chromosome in 40% of the cells [1]. 

While it still isn’t safe to test on humans in-vitro, the fact that they managed to do this at all is very remarkable. The scientists are now working on improving the technology’s ability to remove the extra Chromosome from most- if not all- human stem cells [1]. 

 Of course, like all CRISPR techniques, there is still a fear that it can have some off-target effects. With this technology, deleting an entire chromosome would have fatal effects on a person. In order for it to be used in humans, in-vitro, it must be virtually guaranteed that this technology will not delete anything other than the extra 21st Chromosome, especially since Down Syndrome isn’t a death sentence unlike many other genetic conditions. 

Personally, if I had Down Syndrome or had a child with Down Syndrome, I would be happy to donate some stem cells for the scientists to run tests on. But, I wouldn’t be comfortable with testing the technology in-vitro until they are basically certain that it won’t delete any other chromosomes, or interfere with other vital cell activities. At the moment, that’s a huge ask. But, at the same time, I’m quite confident that scientists will figure out how to make this technology more effective, and how to make it less dangerous. 

References:

1. Arnold, P., Clark, G., & Egan, R. (2026, April 14). CRISPR takes a bold leap toward silencing down Syndrome’s extra chromosome. CRISPR takes a bold leap toward silencing Down syndrome’s extra chromosome. https://medicalxpress.com/news/2026-04-crispr-bold-silencing-syndrome-extra.html. 

1. Lian, G., Khabazeh, A., & Sheen, V. (2026). A modified CRISPR/Cas9 approach in silencing the triplication in down syndrome: A treatment path XISTs. Proceedings of the National Academy of Sciences - PNAS, 123(16), e2517953123. https://doi.org/10.1073/pnas.2517953123.