Yale University researchers have found a new method to create lasting genetic changes within human cells, opening up the possibility of new treatments for inherited diseases like sickle cell anemia.
The researchers corrected a specific defect within a human gene that causes the blood disorder thalassemia, researchers reported in a study to be published online in the journal Proceedings of the National Academy of Sciences USA. The disease affects production of hemoglobin, the molecule in red blood cells that carries oxygen to the body.
Scientists in the laboratory of Peter Glazer, professor and chair of the Department of Therapeutic Radiology and professor of genetics at the Yale School of Medicine were also able to slip a sort of genetic repair kit into blood stem cells. In theory, repairs to these hematopoietic progenitor cells would enable the body to produce healthy red blood cells indefinitely
Genetic diseases like thalassemia and sickle cell anemia are particularly problematic to treat because defects are carried within DNA of every cell in the body. Glazer’s laboratory team, headed by Joanna Chin, created a series of artificial DNA molecules designed to bind to specific locations in the genome. These molecules, called triplex-forming oligonucleotides, trigger the DNA’s own repair system, resulting in potentially permanent correction of genetic defects.
In the past, gene-based therapies have met with limited successes in part because of difficulties finding ways to insert a new version of an entire gene into human cells and to have that new gene stay active for a long time. Glazer said their technique avoids some of these pitfalls because it employs oligonucleotides that are short, synthetic DNA molecules that are easier to insert into cells and do not require viruses for their delivery. Importantly, the new technique fixes the defect in the existing gene so it can be expressed in a natural manner, Glazer noted.
Other researchers on the study from Yale contributing to the study were Jean Y. Kuan, Pallavi. S. Lonkar and Diane Krause. Researchers from the National Institute on Aging, University of Kansas, University of Copenhagen in Denmark, and University of North Carolina also were contributing authors.
The work was funded by the National Institutes of Health.
Peter Glazer
yale