CRISPR-Cas9 Successfully Removes Extra Chromosome 21 in Landmark Study, Offering New Hope for Down Syndrome Treatment
A groundbreaking new study demonstrates the potential of CRISPR-Cas9 gene editing to correct the genetic anomaly underlying Down syndrome, marking a significant milestone in the pursuit of effective treatments for the condition.
Down syndrome, clinically known as trisomy 21, affects approximately 1 in every 700 births in the United States. The condition arises from the presence of an extra copy of chromosome 21, disrupting normal cellular function and leading to a range of health and developmental challenges, including intellectual disabilities, congenital heart defects, and an increased risk of Alzheimer’s disease. Now, researchers at Mie University in Japan have achieved a critical breakthrough: the selective removal of this extra chromosome from human cells in a laboratory setting.
The research, led by Ryotaro Hashizume, showcases the power of the CRISPR-Cas9 gene-editing tool. This technology utilizes a specialized enzyme to target and precisely cut DNA sequences. In this instance, the team engineered CRISPR guide molecules to identify and remove only the extra copy of chromosome 21 – a process termed allele-specific editing.
“We designed our CRISPR system to target the extra chromosome without affecting the normal pair,” Hashizume explained. “Our goal was to remove the surplus material and see whether the cell’s gene expression returned to typical levels.”
Initial experiments were conducted on stem cells grown in the lab. Following the removal of the extra chromosome, scientists observed a normalization of gene expression and protein production. Notably, genes crucial for nervous system development exhibited increased activity, while those linked to metabolism were suppressed – findings consistent with previous research indicating that trisomy 21 disrupts fetal brain development.
The team expanded their trials to include skin fibroblasts – mature, non-stem cells obtained from individuals with Down syndrome. The extra chromosome was successfully removed in a significant number of treated cells, further bolstering the promise of this approach.
“These results are particularly promising,” Hashizume noted. “Even in differentiated cells, we observed correction of the chromosomal abnormality, which opens the door to broader applications across various tissue types.” Corrected cells demonstrated improved biological function, exhibiting faster growth rates and shorter doubling times compared to untreated cells. Furthermore, they produced fewer reactive oxygen species – harmful byproducts associated with cellular stress and aging – indicating enhanced mitochondrial function and overall cell health.
However, the process isn’t without its hurdles. Researchers acknowledged that some CRISPR cuts inadvertently affected healthy chromosomes, raising concerns about potential off-target effects. To mitigate this risk, the team is actively refining the guidance molecules to ensure precise targeting of only the extra chromosome 21.
“Precision is critical,” Hashizume emphasized. “We are optimizing our targeting strategy and evaluating how these edited cells behave over time in real-world biological systems.” Experts believe that if the technique can be refined for safety and reliability, it could pave the way for regenerative medicine applications, such as stem-cell-based therapies designed to replace or repair damaged tissues in individuals with Down syndrome.
The potential of genetically addressing Down syndrome also raises complex ethical considerations. The experience in Iceland, where the condition has become rare due to widespread prenatal screening and subsequent abortion decisions, has ignited international debate. “When we start listening to what people with Down syndrome themselves have to say about this … they find it disturbing … and we hear the same stories from their families,” stated Astridur Stefansdottir, a medical doctor and professor in applied ethics at the University of Iceland, in an interview with ABC News Australia.
The Japanese research team has clarified that their objective is not to eliminate Down syndrome from society, but rather to deepen understanding of how genetic editing can alleviate the biological challenges associated with the condition. Down syndrome is frequently linked to a spectrum of medical complications, including a nearly 50% incidence of congenital heart defects – most commonly an atrioventricular septal defect – as well as increased risks of gastrointestinal issues, thyroid dysfunction, immune system irregularities, and early-onset Alzheimer’s disease.
Scientists hypothesize that the extra chromosome 21 contributes to increased production of amyloid precursor protein, leading to the formation of amyloid beta plaque in the brain – a hallmark of Alzheimer’s disease. This contributes to a three-to-five times higher risk of dementia in individuals with Down syndrome compared to the general population. By removing the extra chromosome, researchers hope to reduce or delay the onset of these comorbidities.
Despite the promising results, experts caution that clinical application remains a distant prospect. “This technique is not ready for use in hospitals or routine medical practice,” Hashizume said. “But it sets a new benchmark for what CRISPR can do — not just editing single genes, but removing entire chromosomes.” The study’s publication in PNAS Nexus represents a significant advancement in chromosome-level gene editing. Future research will focus on long-term monitoring of modified cells and exploring the potential for in vivo applications.
In related news, scientists at the University of Florida (UF) recently unveiled a groundbreaking mRNA vaccine designed to activate the immune system to target and destroy various types of tumors, offering a potential new avenue for universal cancer treatment.
The Mie University team’s work represents a pivotal step toward a future where the biological burdens of Down syndrome can be effectively addressed, offering hope for improved health and quality of life for individuals living with the condition.
