How Gene Therapy Works

Diseases Treated With Gene Therapies

In the wake of Jesse Gelsinger's death, the FDA banned James Wilson from conducting gene-therapy experiments using human subjects. Other researchers, however, didn't operate under those same restrictions.

In 2007, Jean Bennett, a molecular geneticist and physician at the University of Pennsylvania School of Medicine, and her husband, Albert Maguire, a retinal surgeon at Children's Hospital of Philadelphia, began a clinical trial to study a gene-therapy treatment for a rare form of blindness known as leber congenital amaurosis (LCA). A mutation in a gene known as RPE65 leads to a deficiency in a protein that's vital to the normal function of the retina. People who lack this protein suffer progressive loss of vision until they lose all sight, usually by the age of 40.

Bennett and Maguire inserted the RPE65 gene into an adeno-associated virus, the kinder, gentler version of adenovirus. They then injected the engineered virus in low doses into the retinas of three patients. The viruses infected the retinal cells, which started churning out the RPE65 protein. Lo and behold, the vision of all three subjects improved, and no nasty side effects -- including dangerous immune responses -- were reported. The team decided to test a larger test population with a stronger dose of the virus. Six more LCA patients received the gene therapy and enjoyed even better results [source: Kaiser].

That puts SCID and LCA into a rarefied category -- diseases successfully treated by gene therapy. And yet geneticists and molecular biologists feel confident there will be more. James Wilson, who continues to contribute to the field, has isolated 120 types of adeno-associated viruses, many of which perform more effectively in some tissues than others. For example, some of these vectors have an affinity for heart tissue, while others have an affinity for cells in the spinal cord and brain. Future research may yield viable treatments for spinal injuries and for diseases such as Parkinson's [source: Neimark].

Researchers are also making great progress with out-of-the-body therapies. In July 2013, the journal Science published the results of two studies investigating the use of lentiviruses as gene therapy vectors. Lentiviruses are retroviruses, but they are unique in their ability to transfer genes efficiently and permanently in both dividing and nondividing cells. Other retroviruses must do their genetic voodoo on dividing cells. Perhaps more important, lentiviruses seem less prone to activating other cancer-related genes when they insert their payload into the host's DNA. When researchers tested lentiviral-based therapy on patients with adrenoleukodystrophy, an X-linked neurodegenerative disease that affects young males, and metachromatic leukodystrophy, a rare neurodegenerative disease caused by mutations in a single gene, they were able to arrest the progression of both diseases with no harmful side effects [source: Cossins].

In the future, other promising gene therapies are sure to emerge, mostly for hereditary diseases, such as cystic fibrosis, muscular dystrophy, sickle cell anemia and hemophilia. Even phenylketonuria may become a thing of the past, something that probably would make Charlie Gordon pretty happy.

Author's Note: How Gene Therapy Works

It's hard not to be impressed by the mechanics of gene therapy -- the snipping, splicing and swapping of DNA. But separating the "Can you?" from the "Should you?" seems a much more daunting task. I suspect that addressing the ethics of gene therapy depends a great deal on whether you or a family member suffers from a rare genetic disorder.

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