Researchers led by Yale University have corrected a gene mutation in mice that causes thalassemia, thus alleviating symptoms of the blood disorder. This could lead to a similar gene therapy to help humans with the condition.
The team identified a protein in bone marrow that can activate stem cells. They combined the protein with synthetic molecules that act like DNA and encased the combo in nanoparticles that they delivered to mice via intravenous injection, according to a statement. The synthetic DNA, known as PNAs, bring about gene editing by binding to the target gene and prompting the cell to repair the mutation.
Thalassemia is characterized by lower-than-normal levels of oxygen-carrying hemoglobin. The researchers found that the treatment corrected the mutation in enough cells to alleviate symptoms.
"The fundamental result here is that with nanoparticles containing PNAs, along with template DNA, and simple IV infusion of molecules, we achieved enough gene editing to effectively cure the anemia in mice that had thalassemia," said Dr. Peter Glazer, a professor of therapeutic radiology and genetics at Yale.
While gene therapy is being floated as a potential treatment for blood disorders such as thalassemia, its success has so far been confined to lab dishes and not in live animals. For example, a group of physicians and researchers recently used CRISPR editing to correct the mutation that causes sickle cell disease in stem cells derived from patients. But because the Yale-led team’s approach uses synthetic DNA, it sidesteps unplanned side effects that can come with other genome-editing methods, such as CRISPR. "We demonstrated we have extremely low off-target effects," Glazer said.