CRISPR Removes Down Syndrome Chromosome in Cells

In a landmark development in genetic research, Japanese scientists have successfully used CRISPR-Cas9 technology to eliminate the extra chromosome responsible for Down syndrome in human cells. The study was led by Dr. Ryotaro Hashizume, a professor at Mie University’s Department of Pathology and Matrix Biology, who headed a multidisciplinary team responsible for experimental design, data analysis, visualization, and authorship. Their work, supported by Mie University’s institutional backing, places the Japanese research community at the forefront of genome editing innovation.

This groundbreaking study demonstrated a “trisomy rescue” technique with a reported success rate of over 30% under specific experimental conditions—offering new hope in the search for therapeutic interventions.

Down syndrome is caused by trisomy 21, a genetic condition in which individuals have three copies of chromosome 21 instead of the usual two. This extra chromosome results in intellectual disabilities, developmental delays, and a variety of health complications. While traditional research has focused on symptom management, this study aims to correct the underlying genetic anomaly.

Published in the peer-reviewed journal *PNAS Nexus* on February 18, 2025, the study outlines how researchers used allele-specific CRISPR-Cas9 to precisely target and cleave the supernumerary chromosome 21 in induced pluripotent stem cells and fibroblasts derived from individuals with Down syndrome.

The base elimination rate using their optimized method (M2-AS × 13) was 13.1%, but this significantly increased to 23.3% when combined with temporary suppression of DNA repair genes like POLQ and LIG4. In some fibroblast samples, the success rate reached up to 30.6%.

Such variability underscores the importance of context and technique, but the core finding remains: CRISPR can remove the extra chromosome in a meaningful number of cells, a feat previously considered nearly impossible.

Removing the extra chromosome wasn’t the only accomplishment. The study also demonstrated that corrected (euploid) cells exhibited normalized gene expression, particularly in genes associated with neurodevelopment and metabolism. These cells showed improved proliferation rates, reduced reactive oxygen species, and restored antioxidant capabilities—indicators of enhanced cellular health.

Gene expression analysis found over 2,800 differentially expressed genes between trisomic and corrected cells. Notably, up-regulated genes were tied to nervous system development, offering potential cognitive benefits, while down-regulated genes were associated with metabolic processes.

This research marks a major milestone in genomic medicine, demonstrating for the first time that it is technically feasible to remove the extra chromosome responsible for Down syndrome and restore normal cellular function. However, while the results are undeniably promising, they remain confined to laboratory settings. Translating this breakthrough into clinical practice—particularly for prenatal or postnatal therapies—will require extensive validation, rigorous safety evaluations, and careful ethical consideration.

A key element of the enhanced success rate involved temporary suppression of DNA repair mechanisms, a technique that may carry unforeseen risks in living organisms. These challenges underscore the need for further research before any human applications can be pursued.

Still, the work of Dr. Hashizume and his team offers a strong foundation for future therapies that could one day transform the lives of individuals with Down syndrome and their families—ushering in a new era of precision genomic medicine.