Correcting Genetic Defects Through Gene Therapy

Primary Immune Deficiency Disease researcher, Dr. David Rawlings, PIDD

Dr. Rawlings is looking for ways to correct primary immune deficiency diseases (PIDD).

It seems like the stuff of science fiction: purposely introduce a virus into the body that inserts the correct version of a gene into cells and thereby corrects a genetic defect.

Through the work of Dr. Dave Rawlings and other researchers around the world, this process, called gene therapy, is moving closer to reality.

Dr. Rawlings is looking for ways to correct primary immune deficiency diseases (PIDD), a range of genetic disorders that impair the immune system's ability to fight infections.

More than 130 different types of PIDD have been identified to date, each caused by a defect in a different gene.

Last year, Dr. Rawlings, who heads Immunology at Children's, successfully showed that gene therapy could correct a form of PIDD known as X-linked Agammaglobulinemia (XLA) in mice for the lifetime of the animal. This finding sets the stage for clinical trials in the future.

But before this happens, researchers must make the virus that restores the gene as safe as possible. "The virus is the delivery system for the healthy gene. We want to have a successful expression of the inserted gene without any other impact on the patient's DNA," he explains.

Dr. Rawlings and his team are working with tissue-culture and animal models to show how this will work.

They have begun similar studies in patients and animals with Wiskott-Aldrich syndrome (WAS), a gene defect that affects many immune cells, including B cells, T cells and platelets.

"We can control the impact of XLA by giving patients antibody transfusions every two to three weeks, but there currently is no effective treatment for Wiskott-Aldrich syndrome.

"Without bone marrow transplants, children with WAS have many infection-related complications and early mortality," says Dr. Rawlings.

The possible applications for gene therapy go far beyond the correction of single gene defects.

"There are more than 30,000 genes in humans, yet mutations in relatively few individual genes lead directly to serious diseases. If you find a gene defect that causes disease, you know it must be an important gene," says Dr. Rawlings.

"If you can use that knowledge to fix a single defect, you may also be able to use this information to develop treatments for other illnesses in which that gene's activity is implicated."