How to Engineer Sustainable Chromosome Changes in Mice

Evolutionary chromosomal changes may take a million years in nature, but researchers are now reporting a novel technique enabling programmable chromosome fusion that has successfully produced mice with genetic changes that occur on a million-year evolutionary scale in the laboratory. The result may provide critical insights into how rearrangements of chromosomes—the tidy packages of organized genes, provided in equal number from each parent, which align and trade or blend traits to produce offspring—influence evolution.

In results published today in Science, the researchers reveal that chromosome-level engineering can be achieved in mammals, and they successfully derived a laboratory house mouse with novel and sustainable karyotype, providing critical insight into how  may influence evolution.

The laboratory house mouse has maintained a standard 40-chromosome karyotype—or the full picture of an organism’s chromosomes—after more than 100 years of artificial breeding,” said co-first author Li Zhikun, researcher in the Chinese Academy of Sciences (CAS) Institute of Zoology and the State Key Laboratory of Stem Cell and Reproductive Biology. “Over longer time scales, however, karyotype changes caused by chromosome rearrangements are common. Rodents have 3.2 to 3.5 rearrangements per million years, whereas primates have 1.6.”

Such small changes may have big impacts, according to Li. In primates, the 1.6 changes are the difference between humans and gorillas. Gorillas have two separate chromosomes whereas in humans they are fused, and a translocation between ancestor human chromosomes produced two different chromosomes in gorillas. At an individual level, fusions or translocations can lead to missing or extra chromosomes or even to such diseases as childhood leukemia.

https://phys.org/news/

Cancer Drug Could Patients Stay Disease-free

In 2010, three patients received an experimental form of immunotherapy for leukemia through a clinical trial at the University of Pennsylvania. Two of the patients went into complete remission—and stayed that way.  The treatment, known as CAR T-cell therapy, is now FDA-approved to treat certain blood cancers. It involves engineering a patient’s own white blood cells to attack cancerous cells and then returning them to the body. Since clinical trials and FDA approval, CAR T-cell therapy has already been used to successfully treat and clear certain cancers. However, CAR T-cell therapy doesn’t lead to lasting remissions for every patient, and it can cause serious side effects. A new report offers clues about why the treatment is sometimes remarkably effective.

The two patients who responded well to CAR T-cell therapy in 2010 remained disease free for over a decade. One of the men, a Californian named Doug Olson, is now 75. The other, William Ludwig, died early last year of COVID-19. Researchers were able to detect CAR T-cells lingering in Olson and Ludwig’s bloodstreams long after their cancers disappeared, although the types of immune cells that persisted were slightly different than anticipated, the team reported in Nature.

Two T-cells (red) attack an oral squamous cancer cell (white)—a fight that’s part of the natural immune response. Clinical researchers are developing a new type of therapy that modifies a patient’s T-cells to better attack cancer

Now we can finally say the word ‘cure’ with CAR T-cells,” Carl June, the principal investigator for the University of Pennsylvania trial, told The New York Times.

Olson and Ludwig were among the earliest recipients of CAR T-cell therapy, allowing clinicians a chance to track the patients’ cells and condition over the past decade. “To use the word ‘cure,’ you really need a long time to follow up to make sure people don’t relapse,” says David Maloney, the medical director of cellular immunotherapy at the Immunotherapy Integrated Research Center at the Fred Hutchinson Cancer Research Center in Seattle. “When we get these people out to 10 and 11 years post-treatment, that encourages us to be a little more forceful in saying that perhaps patients are cured in some cases.”

 

Source: https://www.popsci.com/