How a gene-editing breakthrough from a Harvard lab saved the life of a girl with leukemia

• A 13-year-old girl was the world's first patient to get a cell therapy called base editing in May.
• The experimental treatment has put her leukemia in remission for six months and counting.

A British teenager's leukemia went into remission after she received an experimental cancer therapy that used a new gene-editing technology called base editing.

Alyssa, 13, was the first-ever patient to receive a base-edited cell therapy after enrolling in a clinical trial in May. A month after the infusion and a subsequent bone-marrow transplant, her cancer, called T-cell acute lymphoblastic leukemia, went into remission, and the Leicester resident remains in remission six months later, the Great Ormond Street Hospital for Children said on December 11.

The dramatic success is an early sign of the potential of base editing, a new technology discovered less than a decade ago in a Harvard University laboratory. Base editing allows scientists to make ultraprecise changes to single letters of DNA in cells. The goal is to make genetic tweaks that could treat or cure diseases.

Beyond leukemia, biotech companies are aiming to use base-editing therapies to treat sickle-cell disease and some types of cardiovascular disease.

In the case of Alyssa, her treatment used base editing to genetically edit T-cells, a type of immune cell, that came from a healthy donor. These cells were edited to allow them to destroy cancerous cells while not attacking her own immune system, and then infused into Alyssa.

"It's our most sophisticated cell engineering so far and paves the way for other new treatments and ultimately better futures for sick children," Dr. Waseem Qasim, a cell- and gene-therapy professor and consultant immunologist at Great Ormond Street Hospital, said in a statement.

Base-editing is an ultraprecise version of CRISPR gene editing

Base editing was discovered in the lab of the Harvard genomics researcher David Liu.

In November 2013, a 26-year-old chemist named Alexis Komor exchanged emails with Liu to figure out a research project, as Insider has reported. Komor and Liu sketched out the base-editing idea in just a few days, which sparked years of research that culminated in their results being published in April 2016 in Nature, a top scientific journal.

That paper has now been cited over 3,400 times and has helped launch multiple biotech companies, including Beam Therapeutics, cofounded by Liu, and Verve Therapeutics.

"It's really crazy that this Frankenstein genome-editing tool put together from all these different parts works so well," Komor previously told Insider.

The technology addresses some of the limitations of CRISPR-Cas9, the Nobel Prize-winning gene-editing technology discovered in 2012.

CRISPR-Cas9 works by cutting a disease-causing gene out of the DNA double helix before stitching it back up. Instead of making a full cut, base editors nick a single strand of DNA, while simultaneously changing a single letter of DNA on the other strand. The cell then repairs that nick and uses the just-edited DNA as its template.

The technology gives researchers an unprecedented level of specificity, being able to make changes to the base elements of genetic code, or the nucleotides nicknamed A, C, G, and T. Researchers often compare base editing to using a pencil and eraser, while the traditional CRISPR system is more like using scissors and glue.

Despite these advantages, base editing also has its limits. Base editors can only change a single letter of genetic code, and researchers haven't yet figured out how to make all the changes. As of now, base editors can make only certain changes to nucleotides, limiting its potential. For instance, base editing can change an A to a G but not an A to a T.

Newer technology, like prime editing, can write and edit longer stretches of letters.

Big Pharma sees 'tremendous potential' in base editing

The potential of base editing doesn't stop with Alyssa, as researchers are starting to test base-editing therapies in a range of conditions. Earlier this month, the FDA cleared a different T-cell therapy that is similar to Alyssa's treatment to start initial human testing.

"Seeing more patients like Alyssa experience remission from this treatment would mean so much both to the researchers who developed base editing, and to the communities of patients who might benefit," Liu told Insider in an email.

Big Pharma has also shown interest, with Pfizer agreeing in January 2022 to pay $300 million up front to collaborate with Beam on several base-editing therapies.

Mikael Dolsten, Pfizer's chief scientific officer, told Insider at the time he anticipates base editing having an impact for large patient populations over time — and not just for rare diseases.

"This is a curative technology and can really transform genetic medicine for the future," Dolsten said. "It has tremendous potential."