What Three Gene-Therapy Deaths Have in Common

In recent months, news came out about several distressing cases that have underscored the risks of gene therapy, which delivers DNA to a patient’s cells to treat disease.

All of these cases have one thing in common that’s not apparent at first glance.

A child in China , enrolled in a clinical trial for gene therapy, died of acute respiratory distress syndrome, in which fluid builds up in the lungs and oxygen cannot enter.

In a separate clinical trial in China, a child died after clots formed in their small blood vessels, likely disrupting the delivery of oxygen to organs such as the kidneys and brain.

And earlier this year, researchers reported that a 5-year-old boy treated in Philadelphia had a brain tumor that was likely caused by gene therapy. (He’s doing okay now.) In each of these cases, the gene therapies relied on a versatile but unpredictable type of virus: adeno-associated virus, or AAV for short.

AAVs are the workhorses of many of the most successful gene therapies in the world.

Scientists modify them so that they can deliver a working copy of particular genes to the body, but cannot replicate and aren’t infectious.

These treatments have transformed a form of spinal muscular atrophy—once the genetic disorder most responsible for infant mortality—into a survivable condition, and have been approved for a devastating enzyme deficiency, muscle-wasting disease, and hemophilia, to name a few.

The terrible outcomes AAVs can cause are rare, but they’re a real risk.

So far, the treatments have been used in small patient groups—the most commonly given one has been received by about 5,000 children since 2019—and focused on diseases that dramatically affect or shorten people’s lives.

But AAV-based gene therapies are being explored for prevalent ailments, including heart disease, high blood pressure, and perhaps even Alzheimer’s.

As the use of gene therapy increases, so might the instances in which it goes dramatically wrong.

The modified AAVs involved in gene therapy each contain a single strand of DNA.

One portion of that strand drives the virus’s ability to get inside cells, and another is the helpful human gene that’s being delivered.