Doctors rewrite baby’s DNA to cure genetic disorder in world first

Experts hailed the ‘totally extraordinary’ success of Crispr technology therapy in saving the life of a child with a rare and potentially fatal liver condition

A baby with an extremely rare and life-threatening genetic disorder has had its DNA rewritten by doctors in a world first that could pave the way for more personalised gene-editing therapies.

Independent experts have hailed the breakthrough as “totally extraordinary” after doctors were able to treat a severe disorder that is suffered by only one in 1.3 million people and kills half of those affected in infancy.

The baby, known as KJ, was born with a condition known as carbamoyl phosphate synthetase 1, or CPS1, deficiency.

Ammonia is created in the body when proteins are processed in the liver. An enzyme in the liver is meant to break this ammonia down into urea, which can then be passed from the body in urine. But in those Babies born with the condition often have to wait until they are old enough for a liver transplant and may have to live on a low-protein diet while they wait, but they may die before they get the chance because high ammonia levels can trigger organ failure and brain swelling.

Researchers from the Children’s Hospital of Philadelphia (CHOP) and the Perelman School of Medicine at the University of Pennsylvania used the Crispr gene-editing technique, which can make precise edits to DNA within living cells, altering its code one letter at a time.

They corrected the fault causing the CPS1 deficiency and used tiny particles of fat to deliver the corrected cells to the liver.

It is the first time that gene-editing technology has been used to create a bespoke therapy for a single patient displaying one specific mutation, rather than using the technique to address a range of mutations behind a particular disease.

The baby received a very low dose of the treatment at six months, which was then increased as he grew older.

“We knew the method used to deliver the gene-editing machinery to the baby’s liver cells allowed us to give the treatment repeatedly — that meant we could start with a low dose that we were sure was safe,” Dr Rebecca Ahrens-Nicklas, a geneticist at CHOP, said.

The child has responded well to the treatment and has been able to eat higher levels of protein. They were also able to effectively fight off a cold and a gastrointestinal illness, a sign that their immune system was strong enough to deal with infections. The baby is likely to need lifelong monitoring.

“The promise of gene therapy that we’ve heard about for decades is coming to fruition, and it’s going to utterly transform the way we approach medicine,” Kiran Musunuru, a professor of cardiology at the University of Pennsylvania, said.

“It seems to me to be a study of the highest quality and totally extraordinary,” said Marc Güell, a professor of synthetic biology at Pompeu Fabra University in Barcelona, who was not involved in the study. “In fact, I was deeply moved to read it. It reflects the great potential of gene editing for therapeutic purposes.”

Gemma Marfany, professor of genetics at the University of Barcelona, said that it was historic, noting: “This is the first case of a fully customised therapy, for a single baby, treated in vivo with a base-editing therapy for a very severe ultra-rare disease.”