New Gene Therapy for "Bubble Boy" Disease Appears to be Safe, Effective

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Early data published in the New England Journal of Medicine suggests that the therapy may avoid the late-developing leukemia seen in a quarter of SCID-X1 patients in previous gene-therapy trials in Europe that took place more than a decade ago. Left untreated, boys with SCID-X1 usually die of infection before their first birthday.

The lab of coauthor Frederic Bushman, PhD, professor of Microbiology, from the Perelman School of Medicine at the University of Pennsylvania, carried out the deep DNA sequencing on patient specimens to track and verify distributions of integration sites of the vector. The vector used in the new trial was engineered to remove molecular signals implicated in cancers in the first trial.

Eight of nine boys recruited to date to the present trial are alive between 12 and 38 months after treatment, with no SCID-X1-associated infections. The gene therapy alone generated functioning immune systems in seven of eight boys. Genetic studies showed that the new viral vector did not lead to vector insertions near known cancer-causing genes, raising cautious hopes about the vector’s long-term safety.

“We showed that fewer cells accumulated with integration sites near cancer genes in the second trial, suggesting that the adverse properties had indeed been engineered out,” explains Bushman “So far there are no clinical adverse events in the present trial — the integration site data has suggested improved safety.”

The modified vector created for the current trial is a self-inactivating gammaretrovirus, designed to deliver its payload effectively while minimizing the chance of inadvertently turning on oncogenes that could lead to leukemia.

The core question of the trial was whether the new self-inactivating viral vector could safely and successfully shuttle a gene called the IL-2 receptor gamma (IL2RG) subunit into the patients’ hematopoietic stem cells. In boys born with SCID-X1, mutations render the IL2RG gene inactive, robbing the children of the ability to produce a functional immune system.

For more information, see the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center’s news release.


Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 17 years, according to U.S. News & World Report‘s survey of research-oriented medical schools. The School is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2013 fiscal year.

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Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2013, Penn Medicine provided $814 million to benefit our community.

PubMed Central

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U.S National Library of Medicine
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