Empty Decoys Divert Antibodies from Neutralizing Gene Therapy

Gene therapy researchers have produced a bioengineered decoy that fools the immune system and prevents it from mistakenly defeating the benefits delivered by a corrective gene.

The decoy was effective in animal studies, and if the approach succeeds in humans, it offers a potential new treatment for genetic diseases such as hemophilia, while advancing the broader field of gene therapy.

"This decoy strategy could be individualized to patients and could greatly expand the population of patients who may benefit from gene therapy," said study leader Katherine A. High, M.D., director of the Center for Cellular and Molecular Therapeutics (CCMT) at The Children's Hospital of Philadelphia. "Right now, 30 to 60 percent of adult patients develop antibodies that block the ability of an intravenously infused vector to reach the target cells in the liver. This approach holds the promise of overcoming this roadblock -- pre-existing antibodies -- and allowing successful intravenous gene therapy in virtually all adult patients."

Previously, in clinical trials, High used adeno-associated virus (AAV) as a vector -- a delivery vehicle -- to ferry a corrective DNA sequence to patients with a mutation causing hemophilia B, the second most common form of the disease. The delivered gene enables the patient to produce a needed blood-clotting factor. AAV does not cause human disease, but because we are routinely exposed to this virus, 30 to 60 percent of people develop antibodies that neutralize AAV if it enters the circulation.