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How Gene Therapy Works

Gene Therapy Safety

Jesse Gelsinger's death stunned the public, and it sent shock waves through the scientific community, too. Geneticists came to the painful realization that gene therapy, while easy to diagram on paper, came loaded with challenges and pitfalls. And it didn't matter how they tackled the problem -- both in- and out-of-the body approaches came with inherent risks.

For in-the-body gene therapy, the biggest issue is the immune system of the patient. The body views adenovirus particles, even those carrying a human gene, as foreign objects. When they enter host cells, the host responds by mounting a counterattack to get rid of the invaders. This is what happened with Jesse Gelsinger. His immune system didn't realize the viruses were trying to be helpful, and it launched a vigorous attack, shutting down his organs in the process. Today, researchers might give Gelsinger lower therapy doses or pretreat him with immunosuppressive drugs. Another option being explored involves "naked" DNA, which refers to a nucleic acid molecule stripped of its viral carrier.

Out-of-the-body therapies relying on retroviruses have their own problems. Remember, retroviruses stitch their DNA into the host chromosome, which is a bit like picking up a short phrase from one sentence and plugging it into a longer sentence. If the insertion doesn't occur in just the right place, the resulting "language" might not make any sense. In some gene therapy trials using retroviruses, patients have developed leukemia and other forms of cancer because inserting one gene disrupts the function of other surrounding genes. This complication has affected several children in the SCID trials, although many of them have beaten the cancer with other therapies.

Because of these issues, the U.S. Food and Drug Administration (FDA) regulates all gene therapy products in the United States through its Center for Biologics Evaluation and Research, or CBER. The center also provides proactive scientific and regulatory advice to medical researchers and manufacturers interested in developing human gene therapy products. Investigators can also turn to the National Institutes of Health for guidance and guidelines when conducting clinical trials with gene therapy.

To date, the center hasn't yet approved any human gene therapy product for sale, although several ongoing trials are producing promising results. Up next, we'll look at a few recent successes in what many believe is the second revolution of gene therapy.