A novel fix-it kit for faulty genes

Blood diseases like thalassemia and sickle cell anemia result from mutations in single genes, but gene-based therapies have met with little success, partly because of difficulties inserting a new version of a gene into human cells and keeping it active over time.

School of Medicine researchers led by Peter M. Glazer, M.D., Ph.D., chair and Robert E. Hunter Professor of Therapeutic Radiology and professor of genetics, have found a new method to create lasting genetic changes within human blood cells, opening up the possibility of new treatments for inherited hematologic diseases.

In the September 9 issue of the Proceedings of the National Academy of Sciences, the researchers report that they used electroporation—in which an electrical field makes cell membranes more permeable—to insert genetic “repair kits” consisting of chemically altered DNA into cells to repair the mutated gene in thalassemia. The faulty gene was fixed, even in human bone marrow cells, meaning that the genetic repair could be inherited by newly generated blood cells.

The new technique avoids traditional gene-therapy pitfalls, Glazer says, because it employs synthetic DNA that is easier to insert into cells and does not require viruses for its delivery.