CRISPR-Cas9,镰刀型红细胞贫血,地中海贫血 z-bio 2021-02-10 412

　　Sickle cell anemia (SCD) and β-thalassemia (TDT) are two common gene-deficient diseases. The common feature is that the globin gene defect causes the synthesis of one or more of the globin peptide chains in hemoglobin to decrease Or cannot be synthesized, resulting in ineffective hemoglobin.

　　At present, the common treatment method is blood transfusion (transfusion of red blood cells) or transfusion of iron chelator, but it is prone to poisoning and cannot cure the disease fundamentally. The only cure method-hematopoietic stem cell transplantation, there is a scarcity of matched donors At the same time, complications after transplantation may also occur at any time. Based on these circumstances, gene therapy, that is, correcting the expression of disease-curing genes at the molecular level, has become a new direction for SCD and TDT therapy.

　　On December 5, 2020, researchers from the Sarsh Cannon Institute and Boston University School of Medicine published an article titled "CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia" in NEJM, demonstrating the use of CRISPR -Cas9 technology edits autologous CD34+ cells, increases fetal hemoglobin expression, and can effectively treat TDT and SCD.

　　Fetal hemoglobin is composed of α-globin and γ-globin. With the production of β-globin and adult hemoglobin, γ-globin decreases postpartum. Studies have found that BCL11A is a repressor of erythrocyte gamma globin expression. Therefore, down-regulating the expression of BCL11A and activating γ-globin can increase hemoglobin content. The experimenters used CPRSPR-Cas9 technology to edit autologous CD34+ cells, specifically targeted to silence the BCL11A gene, and reactivated the production of fetal hemoglobin.

　　Dr. Haydar Frangoul of the Sarah Cannon Institute said: "What we are doing is turning off the switch and making the cells think they are back in the womb, thereby recreating fetal hemoglobin."

　　After evaluating gene-edited CD34+ cells from 10 healthy donors, the researchers found that the fetal hemoglobin level rose to 29±10.8%, while the unedited cells were 10.5±5.2%.

　　In the clinical trial, the researchers selected a 19-year-old female patient with TDT and a 33-year-old female patient with SCD to infuse gene-edited autologous CD34+ cells. Within 12 months, the patients’ bone marrow and blood were allele-edited. The efficiency remains high, and over 99% of the red blood cells in the blood circulation express fetal hemoglobin. At present, both patients have reported that they no longer need blood transfusion.

　　CRISPR-Cas9 technology realizes precise targeted gene therapy, providing the possibility of successful cure of genetic defect diseases in the future. Of course, the application of CRISPR-Cas9 technology in the field of diseases has just begun.