Genome Editing to Reverse “Bubble Boy” Syndrome

A new kind of gene therapy which involves editing, rather than replacing, faulty genes in sick people, is being used experimentally in patients. The latest report shows how scientists can correct a broken gene as it sits in the patient’s genome. How the health of the patient, a 4-month old infant, will change is yet to be reported.

Genome editing technology is considered a promising new tool for curing disease. For decades, gene therapy has meant that a virus delivers a functional copy of a gene that is dysfunctional in a patient. The dysfunctional copy remains and the therapeutic version typically remains separate from the rest of the genome.

The technology has drawbacks. First, by sitting outside of the genome, the activity of therapeutic gene isn’t regulated properly. In some cases, the therapeutic copy is delivered by a retrovirus the plunks the new gene down near randomly in the patients genome, which risks disrupting another gene, potentially causing cells to turn cancerous. Second, some diseases, such as Huntington’s, can’t be treated this way because the broken copy of the gene causes harm. To treat these kinds of conditions, the original copy of the gene must be corrected. Using genome editing to repair genes could circumvent these issues (see “Genome Surgery”).

In the new study, published today in the journal Nature, researchers in Milan treated a condition known as Severe Combined Immunodeficiency Syndrome, or SCID (this condition is sometimes referred to as “bubble boy disease” because children afflicted may live in protected environments because the risk of death from infectious disease is extremely likely). Children with this genetic condition have been treated with the additive gene therapy method in the past, and some suffered leukemia-like diseases as a side effect (see “The Glimmering Promise of Gene Therapy”). In the new report, researchers describe treating a single infant with zinc-finger nucleases designed to repair a defective copy of an important immune system gene.

The report does not look at the long term health effects for the infant. But the team shows that the genome editing did reconstitute a functional copy of the immune system gene in a small fraction of bone marrow cells (which give rise to immune cells). “This work is undoubtedly a step towards using gene repair for gene therapy,” writes immunologist Alain Fischer in an accompany article also published in Nature. Fischer led the first successful gene therapy trials for SCID patients.

In March, researchers reported an even more dramatic example of gene repair. Scientists used zinc fingers to engineer the immune cells of patients with HIV to resist the virus (see “Can Gene Therapy Cure HIV?”). In a few patients, the amount of virus in the blood decreased and in one patient, the virus could no longer be found.