Magazine article Science News

Gene Therapy Escapes the Immune Response

Magazine article Science News

Gene Therapy Escapes the Immune Response

Article excerpt

Lately, enthusiasm over gene therapy has given way to skepticism. The National Institutes of Health, for instance, is evaluating whether investigators are rushing too quickly to start human trials of gene therapy.

As this reflection goes on, researchers continue to challenge the barriers to gene therapy's success. According to a report in the September Nature Medicine, investigators have taken a crucial step toward overcoming one such barrier. They've found a way to sneak genes past the body's defenses more than once, a feat that might allow repeated gene therapy efforts in the same patient.

One of the largest obstacles to gene therapy is the immune response, a usually welcome defense against viruses or bacteria. Researchers often use crippled viruses, ones that can't replicate, to ferry healing genes into cells. For example, adenoviruses, which cause respiratory infections, are a popular method of targeting the lungs.

But the immune system makes no distinction between good and bad viruses. In animals, immune cells eventually kill any cells infected by the engineered adenoviruses, limiting how long the genes that they have carried in will be active. Moreover, the immune response generates antibodies that neutralize adenoviruses, preventing gene therapists from using that delivery method more than once. That's a major problem for diseases, such as cystic fibrosis, where patients will need repeat doses of curative genes, says James M. Wilson of the University of Pennsylvania Medical Center in Philadelphia.

Therapists are therefore scrambling for ideas to sneak gene-carrying viruses past the immune system. One method may be to briefly suppress immune responses when they introduce gene-loaded viruses, Wilson and coworkers report in Nature Medicine.

Previously, Wilson's group injected mice with antibodies that target CD4 cells, a type of white blood cells active in immunity. …

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