How Gene Therapy Works

In-the-body Gene Therapy

The second common way to administer gene therapy is to inject the gene-carrying virus directly into the region that has defective cells. James Wilson, professor of pathology and laboratory medicine at the University of Pennsylvania, pioneered this so-called "in-the-body" gene therapy in the 1990s. He used adenovirus as his vector, but he weakened it to limit the immune response in the recipient. In early tests, his modified virus seemed to cause no harm at all -- not even sniffles -- in test subjects. That meant it could deliver genes reliably with few side effects.

In 1999, he led a phase I clinical trial to test adenovirus-based therapy for the treatment of a rare genetic disorder called ornithine transcarbamylase (OTC) deficiency. OTC is an enzyme that helps the body break down excess nitrogen. Without it, ammonia levels increase until the brain becomes poisoned. A single gene on the X chromosome codes for the enzyme, making it an ideal candidate for the experimental therapy. Wilson inserted the OTC gene into weakened adenovirus particles and then injected those into the livers of 18 patients [source: Neimark].

The idea was simple: The virus would infect the liver cells, which would then proceed to replicate the OTC gene and begin manufacturing the enzyme. Unfortunately, one of the patients, 18-year-old Jesse Gelsinger, died just three days after receiving his injection of the engineered virus. Scientists now think that Gelsinger's body mounted a massive immune response, leading to widespread organ failure. That's just one of the risks of gene therapy, as we'll see on the next page.