In April 2016, Waseem Qasim, professor of cell and gene therapy, was intrigued by a New scientific articles 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, describes a version of Crispr gene editing that allows for more precise changes than ever before. “It looks like science fiction has arrived,” says Qasim, a lecturer at University College London.
The genetic code of all living things is made up of a chain of four chemical bases: A, C, G, and T. These bases combine to form the double helix structure of DNA. Traditional Crispr and previous gene-editing methods work by cutting the double helix of DNA to remove, for example, a disease-causing gene. Base editing, on the other hand, is simply swapping one chemical base with another to correct a mutation or disable a gene. The first base editor that Liu’s lab describes can convert C to T. Others have been invented since.
Scientists immediately recognized the value of base editing. Many genetic diseases, such as cystic fibrosis and sickle cell anemia, are caused by single changes in DNA. Now, those mutations could theoretically be overcome by converting one base to another. Qasim and his team want 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 they were extremely effective at inducing genetic changes to cells. in the laboratory. Over the next six years, they worked to improve the technology, and in May they put it to the final test, using it to treat leukemia patients in the hope of curing the cancer. for her. This is the first time this new form of gene editing has been used to treat humans.
Patient Alyssa, 13, was diagnosed with a rare and malignant cancer called T-cell leukemia in May 2021. As an important part of the immune system, T cells usually protects 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 is eligible to participate in the experimental base-editing therapy trial. 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 cells. The edits allow the donor T cells to bypass the body’s defenses, recognize a certain receptor on leukemia cells, and destroy the cancer. Doctors at the Great Ormond Street Institute for Children’s 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 of cancer immunotherapy. In some patients, it can be life-threatening, but Alyssa’s symptoms were mild and she recovered quickly, Qasim said. One month after the infusion, her cancer was in remission and she continues to be healthy. “We have confirmed the extent of the disease remains undetectable,” said Qasim. He present these preliminary results earlier this month at the American Society of Hematology meeting in New Orleans. (These findings have yet to be published in a peer-reviewed journal.)
