A More Elegant Form of Gene Editing Progresses to Human Testing

In April 2016, Waseem Qasim, a professor of cell and gene therapy, was captivated by a new scientific paper that described a revolutionary way to manipulate DNA: base editing. The paper, published by David Liu’s lab at the Broad Institute of MIT and Harvard, described a version of Crispr gene editing that allowed for more precise changes than ever before. “It seemed like science fiction had arrived,” says Qasim, who teaches at University College London.

The genetic code of every living thing is made up of a string composed of four chemical bases: A, C, G, and T. These pair up to form the double helix structure of DNA. Traditional Crispr and previous gene editing methods work by cutting DNA’s double-stranded helix in order to knock out a disease-causing gene, for instance. Base editing, on the other hand, simply swaps one chemical base for another in order to correct a mutation or disable a gene. The first base editor that Liu’s lab described could convert a C to a T. Others have been invented since. 

Scientists immediately recognized the value of base editing. Many inherited diseases, such as cystic fibrosis and sickle cell anemia, are caused by single-base changes in DNA. Now those mutations could, in theory, be fixed by converting one base for another. Qasim and his team wanted to use base editing for another purpose: altering immune cells in an attempt to treat cancer.

Using Liu’s paper as a guide, Qasim and his team created their own base editors and found that they were incredibly efficient at making genetic changes to cells in the lab. Over the next six years, they worked to improve the technology, and in May, they put it to the ultimate test, using it to treat a leukemia patient in hopes of curing her cancer. It was the first time this new form of gene editing was used to treat a human being.

The patient, a 13-year-old named Alyssa, was diagnosed with a rare and aggressive type of cancer called T-cell leukemia in May 2021. An important part of the immune system, T cells normally protect the body from infection. But in T-cell leukemia, they grow uncontrollably. Doctors tried to treat Alyssa with chemotherapy and a bone marrow transplant, but her cancer came back.

With no other treatment options left, Alyssa was eligible for a trial testing the experimental base editing therapy. Qasim and his team collected T cells from a healthy donor and used base editing to make four separate changes—all C to T base conversions—to the cells. The edits allowed the donor T cells to slip past the body’s defenses, recognize a certain receptor on leukemia cells, and kill the cancer. Doctors at Great Ormond Street Institute of Child Health, part of University College London, then infused the edited cells into Alyssa’s bloodstream. 

After receiving the edited cells, Alyssa experienced an inflammatory side effect known as cytokine release syndrome, a common side effect with cancer immunotherapy. In some patients, it can be life-threatening, but Alyssa’s symptoms were mild and she recovered quickly, Qasim says. A month after her infusion, her cancer was in remission, and she continues to do well. “We’ve confirmed the disease levels are still undetectable,” Qasim says. He presented these preliminary results earlier this month at the American Society of Hematology meeting in New Orleans. (The findings have not yet been published in a peer-reviewed journal.)