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Scientists race to lab-grow 'golden blood' for rare Rh null patients
Only about 50 people worldwide possess Rh null blood-the rarest known type-making transfusions nearly impossible to source. Now, researchers are pioneering lab-grown solutions to bridge the gap, with breakthroughs in gene editing and stem cell technology offering hope for universal compatibility.
The challenge of Rh null blood
Rh null blood lacks all 50 antigens in the Rhesus (Rh) system, a genetic anomaly so rare it appears in just one in six million people. While recipients with this blood type cannot safely accept donations from others, their own blood-particularly type O Rh null-is uniquely compatible with all Rh-positive and Rh-negative patients. This versatility has earned it the moniker "golden blood" among researchers.
Currently, those with Rh null are advised to bank their own blood for emergencies. But with global demand for universal donor blood rising-especially in trauma care where a patient's blood type may be unknown-scientists are turning to laboratories to manufacture it.
"Rh antigens trigger a large immune response. If you have none at all, there's nothing to react to in terms of Rh. But other blood groups still matter."
Ash Toye, professor of cell biology, University of Bristol
Gene editing and stem cells: Two paths forward
Researchers are exploring dual approaches to produce Rh null blood artificially. In 2018, a team led by Toye used CRISPR-Cas9 to delete genes coding for five major antigen groups-including ABO, Rh, Kell, Duffy, and GPB-in lab-grown red blood cells. The result: an "ultra-compatible" cell line theoretically safe for nearly any recipient, including those with the Bombay phenotype (one in four million people).
Meanwhile, other labs are leveraging stem cells. At Laval University (Canada), scientists edited A-positive donor stem cells to remove A and Rh antigens, yielding O Rh null precursors. Similarly, a Barcelona team converted Rh null stem cells from type A to type O, broadening compatibility. However, scaling production remains a hurdle, as lab conditions struggle to replicate the bone marrow's intricate signals for red blood cell maturation.
"Creating Rh null blood can disrupt cell growth. The membrane might destabilize, or production efficiency could drop."
Gregory Denomme, immunologist and medical affairs director, Grifols Diagnostic Solutions
Clinical trials and the road ahead
Toye's RESTORE trial, the first to test lab-grown red blood cells in healthy volunteers, marks a critical step-though the cells used were not gene-edited. The process, a decade in development, underscores the complexity of translating research into clinical practice.
For now, traditional donations remain the backbone of transfusion medicine. Yet for Rh null individuals, lab-grown alternatives could be transformative. Toye's spin-off, Scarlet Therapeutics, is building a rare-blood cell bank, prioritizing donors with minimal antigens to maximize compatibility. Gene editing, he notes, remains a "future option" if natural selection falls short.
Key obstacles
- Maturation challenges: Lab-grown cells often fail to fully develop, risking inefficacy.
- Regulatory hurdles: Gene-edited blood faces stringent approval processes.
- Cost: Synthetic production is vastly more expensive than traditional donation.
Why 'golden blood' matters beyond rarity
Beyond emergencies, Rh null research could revolutionize transfusion medicine by:
- Reducing allergic reactions in patients with multiple antibodies.
- Enabling safer transfusions for ethnic minorities, who often face antigen mismatches in donor pools.
- Serving as a template for "universal" blood-though Toye cautions that "no single product will ever cover 100% of cases" due to the 366+ known antigens.
As Denomme puts it: "The goal isn't just to replace donations, but to fill the gaps where nature-and geography-leave patients vulnerable."
