An experimental gene-editing cell therapy for sickle cell disease has shown encouraging initial results in a multicenter Phase 1 and Phase 2 clinical trial. The clinical trial is the first in which CRISPR-Cas12 is used to edit human cells. Cas12 has been shown in preclinical research to be more effective for gene editing as it is a single RNA endonuclease compared with Cas9, which is a double RNA endonuclease. The aim was to make gene editing more precise, more efficient and targeted directly to G1 and G2 hemoglobin, added directly instead of a different activator, so that it mimics exactly what happens in nature with fetal hemoglobin. The four patients in the clinical trial were able to go through all the phases of the study, from mobilization to chemotherapy and perfusion of the CD34-modified cells. They were then transplanted, and the patients can now be transfusion-independent. So far, all four patients have experienced no pain attacks, and any side effects noted were mainly related to the busulfan used in the chemotherapy regimen. All four patients were able to achieve a fetal hemoglobin of over 40% in around 3-4 months. They all had hemoglobin in the normal range from about 3 months post-transplant. Hemolysis markers also normalized, which is a major finding.
