I think it's an open question. After this treatment, the patient's red blood cells will be producing a new protein that they have never produced before. This protein only differs from the previous one by one amino acid, so the question becomes how sensitive the immune system is to such a change. Given that the immune system has some difficulty recognizing cancer cells with multiple protein-coding mutations in them, I think it's likely that a single amino acid change will fly under the radar and not require any immune suppression, at least for the vast majority of recipients of this treatment.

Wiping out the bone marrow should also (essentially) reset the immune system IIRC.

Bone marrow transplant (BMT) recipients can still experience graft versus host disease (GVHD) which is when the transplanted marrow produces healthy cells that start to attack the host body.

Besides GVHD, it is like you said. BMT patients are one of the few transplant types that can eventually come off of immuno-suppressants with a successful transplant. The patient's original bone marrow is supposed to be wiped out by chemotherapy (and sometimes some radiation) to make room for the new marrow transplant.

Can we take a moment to appreciate the straightforward naming of graft-versus-host disease? I couldn't find the history of its discovery beyond this (https://www.sciencedirect.com/science/article/abs/pii/S03014...) and even there, I couldn't find any indication of how it came to receive that name specifically, but it's much better than "[scientist's name]'s disease/syndrome" that we keep running into because people want credits at the expense of accessibility of knowledge.

Yes, but T-cells learn to distinguish self from non-self in the thymus, and I don't believe this treatment alters the hemoglobin gene sequence in the thymal epithelial cells. Of course, the thymus, like the rest of the body, will be served by red blood cells containing the new hemoglobin gene, but I'm not sure if this alone is sufficient for immature T-cells in the thymus to learn it as a self protein.

My understanding is that the "fixed" red blood cells antigens would be the same so the T-cell would not be triggered.

All the antigens would be identical except those derived from the modified gene. This tiny difference probably is pretty likely to escape detection, but not 100% guaranteed.

The fundamental idea of using the donor's own stem cells is known as an Autologous Stem Cell Transplant and has existed for a while. It is used as therapy for a fair number of blood cancers (e.g. multiple myeloma or a few leukemias).

Using "something" to manipulate the donor cells has also been done for these autologous HSCTs. I know of "CAR T cell therapy", but there are likely others. ( https://www.cancer.gov/about-cancer/treatment/research/car-t... )

I think some small number of autologous HSCT recipients require immunosuppressants, but from what I remember the number is very very small. (Allogenic HSCT recipients, who receive cells from a different person, are _much_ more likely to require lifetime immunosuppressants.)

It's super cool that they're able to treat genetic diseases this way!