The world’s rarest blood type, dubbed “golden blood," has been found in just 50 people worldwide, and now scientists are racing to grow it in the lab.
Known as Rh-null, this ultra-rare type lacks all Rh antigens, making it a potential game-changer for patients with rare blood disorders.
At about 1 in 6 million, Rh-null isn’t just rare, it’s medically priceless. It can be given to almost anyone with complex Rh profiles, making it a lifeline in critical transfusions.
But there’s a problem: it’s almost impossible to find.
Why Rh-null is the holy grail of blood types
Rh-null blood lacks all 50+ known Rh antigens, which normally help the body recognize its own blood.
Most people know their ABO type - A, B, AB, or O - and whether they’re Rh-positive or negative based on the presence of the RhD protein. But RhD is just one of many Rh antigens.
“Rh [antigens trigger] a large immune response, and so if you have none of [them] at all, then essentially there's nothing to react to in terms of Rh,” explained Ash Toye, professor of cell biology at the University of Bristol, per BBC.
“If you were type O and Rh null, then that's pretty universal. But there are still other blood groups that you still have to consider," Toye added.
Because it lacks all Rh antigens, Rh-null blood is only safe for others with the same rare type. That’s why people who have it are often told to freeze their own blood in case of emergencies. But while it’s risky for them to receive blood, their blood is extremely useful to others.
From gene editing to lab-grown blood banks
Back in 2018, Toye and his team used CRISPR-Cas9 gene editing to recreate Rh-null blood by deleting the genes responsible for five of the most problematic blood group antigens, including ABO, Rh, Kell, Duffy, and GPB.
The resulting blood was ultra-compatible, even for people with extremely rare types like the Bombay phenotype.
“We worked out if we knocked out five, then that would create an ultra-compatible cell, because it had five of the most problematic blood groups removed,” Toye said. But turning this achievement into a widely available medical solution is easier said than done.
Gene editing remains controversial and heavily regulated. To move forward more practically, Toye co-founded Scarlet Therapeutics, a company using stem cells from rare donors, including those with Rh-null, to create permanent lab-grown blood supplies.
“If we can do it without editing, then great, but editing is an option for us,” Toye said. “Part of what we're doing is we're carefully selecting donors to try and make all of their antigens as compatible as possible for most people. Then probably we'll have to gene edit to make it compatible for everybody.”
Researchers in Canada, Spain, and the US have joined the race, using a range of stem cells, including those already preprogrammed to become blood cells, to replicate Rh-null in controlled lab settings.
In one study, scientists at Laval University used CRISPR to delete A and Rh antigens from A-positive blood, creating O Rh-null immature cells. Another team in Barcelona transformed Rh-null donor cells from type A to type O.
But growing mature red blood cells outside the body remains a major hurdle.
“There is the added problem that when creating Rh null or any other null blood type, the growth and maturation of the red blood cells can be perturbed," said immunologist Gregory Denomme, now at Grifols Diagnostic Solutions.
“Producing specific blood group genes might result in the cell membrane falling apart, or a loss of producing red blood cells efficiently in cell culture," he added.
Toye is currently co-leading the RESTORE trial - the first human clinical study testing lab-grown red blood cells made from donor stem cells. These cells weren’t gene-edited, but it still took a decade of research to get to this point.
“At the moment, taking blood out of somebody’s arm is so much more efficient and cost-effective, and so we will need blood donors for the foreseeable future,” Toye said. “But for people with rare blood types where there’s very few other donors, if we can grow them more blood, that would be really exciting.”