Base Editing: Revolutionary Therapy Clears Girl's Incurable Cancer

A teenage girl's incurable cancer has been cleared from her body in the first use of a revolutionary new type of medicine.

All other treatments for Alyssa's leukaemia had failed.

So doctors at Great Ormond Street Hospital used "base editing" to perform a feat of biological engineering to build her a new living drug.

Six months later the cancer is undetectable, but Alyssa is still being monitored in case it comes back.

Alyssa, who is 13 and from Leicester, was diagnosed with T-cell acute lymphoblastic leukaemia in May last year.

T-cells are supposed to be the body's guardians - seeking out and destroying threats - but for Alyssa they had become the danger and were growing out of control.

Her cancer was aggressive. Chemotherapy, and then a bone-marrow transplant, were unable to rid it from her body.

Without the experimental medicine, the only option left would have been merely to make Alyssa as comfortable as possible.

"Eventually I would have passed away," said Alyssa. Her mum, Kiona, said this time last year she had been dreading Christmas, "thinking this is our last with her". And then she "just cried" through her daughter's 13th birthday in January.

What happened next would have been unthinkable just a few years ago and has been made possible by incredible advances in genetics.

The team at Great Ormond Street used a technology called base editing, which was invented only six years ago.

Bases are the language of life. The four types of base - adenine (A), cytosine (C), guanine (G) and thymine (T) - are the building blocks of our genetic code. Just as letters in the alphabet spell out words that carry meaning, the billions of bases in our DNA spell out the instruction manual for our body.

Base editing allows scientists to zoom to a precise part of the genetic code and then alter the molecular structure of just one base, converting it into another and changing the genetic instructions.

The large team of doctors and scientists used this tool to engineer a new type of T-cell that was capable of hunting down and killing Alyssa's cancerous T-cells.

They started with healthy T-cells that came from a donor and set about modifying them.

The first base edit disabled the T-cells targeting mechanism so they would not assault Alyssa's body

The second removed a chemical marking, called CD7, which is on all T-cells

The third edit was an invisibility cloak that prevented the cells being killed by a chemotherapy drug

The final stage of genetic modification instructed the T-cells to go hunting for anything with the CD7 marking on it so that it would destroy every T-cell in her body - including the cancerous ones. That's why this marking has to be removed from the therapy - otherwise it would just destroy itself.

If the therapy works, Alyssa's immune system - including T-cells - will be rebuilt with the second bone-marrow transplant.

- BBC