A donation of healthy blood stem cells can be a game-changer for leukemia sufferers. However, this kind of treatment places a heavy burden on the body, as the patient’s own blood stem cells must first be removed by means of chemotherapy before the new, healthy ones can be injected.
The start-up Cimeio Therapeutics wants to make blood stem cell transplants easier on the body. At the core of this vision is an approach developed by Dr. Romina Matter-Marone, Dr. Rosalba Lepore and Professor Lukas Jeker from the Department of Biomedicine at the University of Basel. The collaboration between Cimeio and Prime Medicine brings the day when this technology is actually used in patients’ treatment a good deal closer.
A soft transition - like a DJ’s sound mixerOn the radio or at a club, the individual songs run seamlessly from one into another; one track fades down in volume while the next one fades up. In the future, Cimeio’s technique will work in a similar way: gently removing the patient’s own, diseased blood stem cells while, in parallel, already starting to establish the new, healthy cells in their body.
This will be made possible by making a targeted change to one of the surface proteins on the donated blood stem cells, so that the patient’s own cells can be distinguished from the donated ones. Therapeutic antibodies will then be able to attack the "original" surface protein on the abnormal blood stem cells and eliminate those cells, while the new cells remain unrecognized and therefore untouched.
The researchers in Basel want to change the "blueprint" for suitable surface proteins in such a way that they can still fulfill their function as before, but that they "look" different to antibodies. They have already worked out what changes will be necessary to achieve this. Now all they need is a way of "rewriting" the genetic blueprint as efficiently and safely as possible.
And this is where Prime Medicine comes in. The company is commercializing a new method of editing genes within the cells. In a similar vein to the CRISPR-Cas9 molecular scissors, which enables targeted cuts to be made in the genetic material, this further development, "Prime Editing," can be imagined as a "Find and Replace" function for the DNA code. The advantage of "Prime Editing" is that the DNA strand is not cut, as with CRISPR-Cas9, meaning that there is a reduced risk for potential damage to the DNA, and any desired change can be introduced.
Very recently, the company was able to prove that this method can rewrite genes in blood stem cells efficiently and precisely, and without unwanted side effects. With Cimeio’s collaboration, this technology can be used to change donated blood stem cells at will.
Repairs within the bodyOne day, it might be possible to edit the genetic material of patients’ own blood stem cells without even removing those cells from their bodies. This could pave the way to a cure for a whole host of inherited blood diseases: the disease-causing genetic defect inside the stem cells could be repaired, and the relevant surface protein altered to stop it being recognized by therapeutic antibodies, all in the same procedure. Then only those blood stem cells that have not been repaired would be weeded out.
Lukas Jeker and his colleagues at the Department of Biomedicine are continuing to work closely with Cimeio. "This has allowed us to study the necessary changes in the surface protein in much finer detail than we could have done on our own in an academic lab," says Jeker. "Were it not for this collaboration, our research results would get published, but we’d have just to hope that someone else would put them into practice for patients." The collaboration between Cimeio and Prime Medicine now means that the most suitable change in the surface protein could be combined with the most suitable editing technology, and used in the treatment of more diseases.