In Down syndrome, a person has an extra copy of chromosome 21. It is still the most common live-birth survivable chromosomal disorder, with an incidence of about 1 in 700.

It is known for more than fifty years that Down syndrome is, at least in most cases, caused by trisomy 21. However, until now, there has been no dependable way to remove this extra chromosome from those cells.

Scientists at Mie University in Japan have made a big step forward in Down syndrome research. They used the CRISPR-Cas9 gene-editing system for the first time to excise that extra copy of chromosome 21 from human cell lines. But this was not just cell behavior; it restored near-normal cellular function, suggesting a basis for future genetic therapies.

CRISPR-Cas9 acts as a more precise DNA-cutting system. Ryotaro Hashizume, an MDA postdoctoral fellow in Dr. Shonyoung Park’s lab, developed custom-designed molecular guides that allow the CRISPR system to home in on only the extra copy of chromosome 21, leaving the healthy ones untouched. After removing the extra chromosome, the cells appeared to function normally and expressed genes in a manner specific for each affected tissue.

After removing an extra chromosome from the edited cells, the cells survived longer, grew faster, and produced fewer harmful metabolic by-products. The physical changes indicate that mitochondrial function was more efficient, resulting in a full restoration of cellular health.

The method was successful with stem and skin cells from patients with Down syndrome, hinting at some generalizability to more differentiated tissues. The research is still limited to the laboratory, but it’s a breakthrough: removing a full extra chromosome from human cells for the first time.

The research team is currently working to perfect the protocol’s safety and accuracy and to prevent natural DNA repair mechanisms from undoing genetic edits in chromosomes.

Journal Reference:

-Ryotaro Hashizume, Sachiko Wakita, Hirofumi Sawada et al. Trisomic rescue via allele-specific multiple chromosome cleavage using CRISPR-Cas9 in trisomy 21 cells. PNAS Nexus. DOI: 10.1093/pnasnexus/pgaf022