Edited stem cells may point to less toxic bone marrow transplants

Researchers have reported a preclinical method that could make stem cell transplantation less dependent on chemotherapy or radiation. The approach, described in Nature, uses genome editing to let therapeutic blood-forming stem cells evade antibodies that are meant to remove a patient’s existing stem cells.

Stem cell transplantation, also known as bone marrow transplantation, and gene therapy can offer long-lasting benefit or possible cures for blood disorders including sickle cell disease, beta-thalassemia, immune deficiencies and some blood cancers, according to Children’s Hospital Boston. Patients usually must first receive intensive conditioning treatment to open space in the bone marrow, often with chemotherapy or radiation that can cause toxic effects across the body.

A targeted way to make room

The study from Pietro Genovese, Ph.D., of the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, and colleagues tested a more selective conditioning strategy. Rather than using DNA-damaging agents broadly, the researchers used antibodies that identify markers on blood-forming stem cells and help clear them from the marrow.

That creates a problem for transplantation. Children’s Hospital Boston said an antibody generally cannot tell the difference between a patient’s original stem cells and therapeutic stem cells infused as treatment. If the antibody remains active after transplant, it can also bind to the new cells and block them from taking hold.

Genovese’s team addressed that issue by editing the therapeutic stem cells. Using precise genome-editing tools, the researchers altered a small antibody recognition site, known as an epitope, on the surface of the donor cells. Children’s Hospital Boston said the change stopped the antibody from binding to the therapeutic cells while preserving the normal role of the protein.

Edited cells survived and expanded

The researchers reported that the protected stem cells survived antibody treatment, settled in the bone marrow and became more enriched over time. The study also combined the protection strategy with therapeutic editing intended to increase fetal hemoglobin, a form of hemoglobin that can compensate for defective adult hemoglobin in sickle cell disease and beta-thalassemia, according to Children’s Hospital Boston.

Gabriele Casirati, MD, an instructor in Genovese’s lab and first author of the study, said avoiding chemotherapy could broaden access to stem cell transplants for patients with less severe disease or for fragile patients considered too sick or too high-risk for transplantation. Casirati said bone marrow transplants are typically reserved for life-threatening disease while also being limited to patients able to tolerate chemotherapy.

The findings suggest two possible uses, according to Children’s Hospital Boston: reducing or replacing chemotherapy in transplant preparation, and using antibodies after transplant to favor protected therapeutic cells until they reach levels likely to provide clinical benefit.

Possible cancer therapy applications

Children’s Hospital Boston said the work builds on earlier Nature research from the same team using epitope editing to protect healthy blood stem cells from cancer immunotherapies, including CAR-T cells and therapeutic antibodies, while allowing those treatments to attack leukemia cells.

Genovese said the current work remains preclinical but points toward curative stem cell therapies with less toxicity, reduced reliance on chemotherapy and greater precision. He said combining targeted biological conditioning with protected therapeutic stem cells offers a framework for safer and more accessible treatments for a range of blood diseases.

The paper, “Non-genotoxic transplantation and in vivo selection through epitope editing,” was published in Nature in 2026. Its DOI is 10.1038/s41586-026-10737-8.

This story draws on original reporting from Medical Xpress.