Scientists have made a significant step towards a gene therapy that may one day be able to stop the extra genetic material that causes Down syndrome
In a move described by scientists as significant, researchers from Beth Israel Deaconess Medical Center and Harvard Medical School have developed a promising gene technology, using a modified version of the popular gene-editing tool CRISPR/Cas9, to target and stop the extra chromosome that causes Down syndrome.
Down syndrome is defined as a genetic condition resulting from the presence of an extra chromosome of type 21, which means there are three copies of hundreds of genes instead of two, leading to problems in growth and the nervous system.
What distinguishes this research from traditional gene therapies that target only one or two genes is that the research team found a way to disable most of the activity of the extra chromosome within the cell at once. Details of this achievement were published in the journal Proceedings of the National Academy of Sciences.
The secret to this technique is inspired by nature itself. In the natural development of biological females, most cells have two X chromosomes. To prevent receiving a double dose of genetic instructions, a gene called XIST automatically switches off one of the chromosomes. Researchers exploited this natural mechanism, using a modified CRISPR/Cas9 technique (which acts as a precise molecular scissors to cut and edit DNA) to insert the XIST gene into the extra chromosome 21, with the goal of completely disabling it.
To test the effectiveness of this method, the team conducted their experiments in the laboratory using human stem cells containing an extra chromosome 21.
After a series of experiments, they found that CRISPR technology was effective in inserting the XIST disabling gene into the precisely targeted location.
As they documented in their research, the modified method greatly improved the fusion efficiency to between 20 and 40%, which is a relatively high percentage for a long gene like XIST.
But the researchers are realistic, acknowledging that treatment based on this technology will not be available in the very near future. However, they emphasize that this discovery represents a real breakthrough and valuable proof of concept, because it indicates the possibility of targeting a specific chromosomal copy within cells without causing widespread damage to other chromosomes.
As the researchers themselves say: "The modified CRISPR method with the XIST gene paves the way for a curative treatment for Down syndrome and other chromosomal abnormalities."
But before this treatment becomes a reality, scientists face additional challenges. Future studies will need to ensure that these gene editing techniques don't cause unintended side effects or accidentally damage other genes. Experiments on animal models will also be necessary, not only to replicate what has been achieved in the lab but also to demonstrate that disabling the extra chromosome can demonstrably improve physical and cognitive health.
