Researchers at the NIH have developed a new and improved viral vector—a virus-based vehicle that delivers therapeutic genes—for use in gene therapy for sickle cell disease. In advanced lab tests using animal models, the new vector was up to 10 times more efficient at incorporating corrective genes into bone marrow stem cells than the conventional vectors currently used, and it had a carrying capacity of up to six times higher, the researchers report.
The development of the new vector could make gene therapy for sickle cell disease much more effective and pave the way for wider use of it as a curative approach for the painful, life-threatening blood disorder, the researchers said.
"Our new vector is an important breakthrough in the field of gene therapy for sickle cell disease," said study senior author John Tisdale, M.D., chief of the Cellular and Molecular Therapeutic Branch at the National Heart, Lung, and Blood Institute (NHLBI). “It’s the new kid on the block and represents a substantial improvement in our ability to produce high capacity, high efficiency vectors for treating this devastating disorder.”
The researchers tested their new ‘forward-oriented’ vectors in mice and monkeys and compared the results to conventional reverse-oriented vectors. They found that the new vectors could transfer a much higher viral load—up to six times more therapeutic beta-globin genes than the conventional vectors—and had four to 10 times higher transduction efficiency, a measure of the ability to incorporate corrective genes into repopulating bone marrow cells. The new vectors also showed a capacity for longevity, remaining in place four years after transplantation. Researchers also found that they could be produced in much higher amounts than the conventional vectors, potentially saving time and lowering costs associated with large-scale vector production.
The study was supported by the NHLBI and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), both part of the NIH. It was published in Nature Communications.