Breakthrough: mRNA Offers Potential for Engineering Bone Marrow Cells in Blood Disorder Treatment
In a groundbreaking development, scientists have made significant progress in using mRNA to modify bone marrow cells and treat blood disorders, including sickle cell disease. The study, conducted by researchers at the Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, outlines a preclinical proof-of-concept model for this innovative approach.
Currently, transplanting bone marrow from healthy donors is a successful treatment for certain blood disorders. However, this procedure comes with its own set of challenges, including the risk of graft-versus-host disease (GvHD) and the need for donors. Additionally, patients undergoing bone marrow transplantation often have to undergo chemotherapy or radiation, which carry their own set of side effects.
In contrast, the new approach described in the study involves modifying hematopoietic stem cells (HSCs) in vivo, using messenger RNA (mRNA) delivery. If successful in human trials, this method could potentially address the limitations of current treatments.
One notable advantage of this technique is its ability to eliminate the need for donor cells and the use of potentially toxic conditioning regimens. Messenger RNA, already recognized for its role in leading COVID-19 vaccines, could be harnessed to enable in vivo editing.
However, a significant challenge lies in targeting specific cells with this technology, particularly when it comes to treating sickle cell disease. To overcome this hurdle, the researchers incorporated anti-CD117 antibodies into the lipid nanoparticles (LNPs) used to deliver the mRNA. By attaching to CD117, a protein found on the surface of HSCs, the antibodies guided the LNPs to the target cells, enabling precise gene editing.
Promisingly, the delivery of the editing system led to near-complete correction of hematopoietic sickle cells. In a preclinical test, the approach resulted in a notable 91.7% increase in functional hemoglobin and a significant reduction in the presence of sickled cells.
Moreover, building on their findings, the researchers utilized the CD117-directed LNPs to develop a drug candidate capable of depleting bone marrow without the need for chemotherapy or radiotherapy. The conditioning LNPs delivered mRNA for PUMA, a protein that initiates cell death. In animal models, this candidate successfully depleted HSCs and facilitated engraftment rates comparable to those observed in patients who had been effectively cured through cell transplants.
This milestone study has the potential to revolutionize the field of blood disorder treatment, offering a novel and more effective approach. While the research is still at the preclinical stage, it provides a strong foundation to advance towards clinical trials and, eventually, human use.
By harnessing the power of mRNA, scientists are paving the way for safer, more targeted therapies. The ability to engineer bone marrow cells in vivo has the potential to reshape the landscape of blood disorder treatment, improving patient outcomes and reducing reliance on donor cells and conditioning regimens. As this groundbreaking research progresses, it holds the promise of transforming the lives of individuals battling blood disorders, bringing hope for a brighter future.
