Brett Smith for redOrbit.com – Your Universe Online

Geneticists from the University of Washington won a key victory in the battle against genetic diseases by successfully removing the extra chromosome 21 from cells derived from a person with Down syndrome, according to the team´s report in the journal Cell Stem Cell.

Down syndrome, also known as trisomy 21, is caused by an extra copy of chromosome 21. In addition to the tell-tale facial features such as an abnormally small chin and almond-shaped eyes, other common features of the genetic illness include heart defects, impaired intellect, premature aging and an increased risk of developing certain types of leukemia.

“We are certainly not proposing that the method we describe would lead to a treatment for Down syndrome,” said study co-author Dr. David Russell, from the University of Washington´s Department of Medicine. “What we are looking at is the possibility that medical scientists could create cell therapies for some of the blood-forming disorders that accompany Down syndrome.”

These treatments could include treating Down syndrome patients with leukemia with genetically-modified stem cells that are derived from their own cells, but without the extra chromosome. Stem cells could be taken from the bone marrow of the patients, doctors could remove the extra chromosome, and then the healthy cells could then be grown and transplanted back into the patient.

Russell added that his team´s findings could not only lead to new treatments for symptoms of the disease, they could also help geneticists to better understand the underlying causes of the disease and any potential treatments or preventions they might be able to pursue.

And beyond its potential relevance for Down syndrome research, the study could also have implications for stem cell research. Stem cell researchers often have difficulty dealing with trisomies — the creation of a third, extra chromosome — in their cell cultures, and the ability to prevent or efficiently remove them could prove invaluable.

To achieve the removal of the extra chromosome, the geneticists used a virus as a vehicle to deliver an engineered gene called TKNEO to a targeted spot on chromosome 21. The researchers used the TKNEO gene because of its predicted response to specific growth conditions. When the modified stem cells were grown in conditions that selected against TKNEO, the cells survived their growth conditions by spontaneously losing chromosome 21. The researchers also tested other survival-based mechanisms, including point mutations, gene silencing, or deletion of the TKNEO. However, chromosome loss was found to be the most common cause for survival.

Russell noted there were many challenges facing this groundbreaking research, but the hard work of his colleague, Dr. Li B. Li of the UW´s Department of Medicine, enabled the team to overcome them.

“Dr. Li´s achievement was a tour de force,” Russell said.

Russell also said the results of the study were important because they resulted in a clean removal of the extra chromosome that did not alter the rest of the genetic code in any way.

“Gene therapy researchers have to be careful that their approaches do not cause gene toxicity,” he said. “This means, for example, that removal of a chromosome must not break or rearrange the remaining genetic code. This method shouldn´t do that.”

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