CRISPR takes important step toward silencing Down syndrome’s extra chromosome

Scientists have taken an important step toward a gene therapy that could one day turn off the extra genetic material that causes Down syndrome (DS). Down syndrome is a genetic condition caused by an extra chromosome 21 (and consequently hundreds of triplicate genes) that leads to developmental and neurological issues. According to the Washington-based National Down Syndrome Society, approximately 1 in every 640 babies in the United States is born with DS. That makes it the most common chromosomal condition.

Traditional gene therapy targets one or two genes, but in this approach, scientists at Beth Israel Deaconess Medical Center and Harvard Medical School found a way to silence much of the extra chromosome's activity in the cell at once.

Details of their research are published in a paper in the journal Proceedings of the National Academy of Sciences.

A new way to use a gene-editing tool

In normal development, every biological female has two X chromosomes in most cells. To prevent a double dose of genetic instructions, a gene called XIST naturally shuts down one of the chromosomes.

The team used a modified version of the gene-editing technique CRISPR/Cas9 (often used like molecular scissors to cut or edit DNA sequences) to insert the XIST gene into the extra chromosome 21 to silence it.

They tested their technique in the lab using human stem cells that contained an extra chromosome 21. After running several experiments, the team found that CRISPR was effective at pasting the XIST silencing gene exactly where it needed to go. As they noted in their paper: "Our modified CRISPR method significantly enhanced the integration efficiency (20 to 40%) of the long XIST gene (14 kb) into an extra chromosome 21."

Future steps

Although this novel approach did not silence chromosomes in the majority of cells, it is a significant breakthrough and a valuable proof-of-concept. It suggests that it may be possible to target a specific chromosome copy in cells without causing widespread damage to others.

Treatment based on this technique may not immediately be around the corner, but it is a significant start, as the scientists acknowledge. "The modified CRISPR method with XIST paves a road for therapeutic treatment for DS and other aneuploidies."

Before that happens, further studies will have to confirm that these changes do not have off-target effects. Additionally, animal models will be needed to replicate not only what the team has done but also to demonstrate that silencing the extra chromosome could improve physical and cognitive health.

Written for you by our author Paul Arnold, edited by Gaby Clark, and fact-checked and reviewed by Robert Egan—this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive. If this reporting matters to you, please consider a donation (especially monthly). You'll get an ad-free account as a thank-you.

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