Hemoglobinopathy treatment effectiveness prediction method

Abstract

The invention relates to a method for treating hemoglobinopathy in an individual. The method comprises the following steps: (a), an evaluation step; the evaluation step comprises the process of evaluating the ability to generate the required level of gamma-globulin or fetal hemoglobin after differentiation of a first population of modified CD34 positive hematopoietic stem / progenitor cells, whereinthe first population of modified CD34 positive HSPC is derived from the individual and modified to reduce the BCL11A function; and (b), a treatment step; the treatment step comprises the process of administering a second population of modified CD34 positive HSPC to the individual; and the modified CD34 positive HSPC is derived from the individual and modified to reduce the BCL11A function. Meanwhile, the invention also relates to a method for treating hemoglobinopathy in the individual, a method of selecting an individual suffering from hemoglobinopathy for treatment with the second population of modified CD34 positive HSPC, and a method of determining whether an individual suffering from hemoglobinopathy is suitable or not suitable for treatment with the second population of modified CD34 positive HSPC derived from the individual and modified to reduce the BCL11A function.

Description

technical field [0001] This application relates to a concomitant prediction method for predicting the effectiveness of gene editing technology in the treatment of hemoglobinopathies. Before treating the disease, this prediction method pre-isolates CD34-positive hematopoietic stem cells from patients, uses gene editing technology to destroy the BCL11A erythroid enhancer site, and predicts the gene-edited BCL11A erythroid in advance by evaluating the degree of up-regulation of γ-globin and fetal hemoglobin expression. Enhancer effectiveness in treating hemoglobinopathies, adjunct to disease therapy. Background technique [0002] Hemoglobinopathy is a group of hereditary blood diseases caused by abnormal hemoglobin molecular structure or abnormal globin peptide chain synthesis. The two main disease types in hemoglobinopathies are beta-thalassemia and sickle cell anemia. The pathogenesis of β-thalassemia is due to gene mutations in the β-globin peptide chain. Most patients hav...

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Problems solved by technology

[0005] Although the BCL11A erythroid enhancer site has been clinically implemented, that is, the clinical Phase 1 / 2 trial of autologous hematopoietic stem cell transplantation developed by gene editing technology for the treatment of β-thalassemia and sickle cell anemia (Clinicaltrials.gov code is NCT03655678, NCT03745287, NCT03432364), but due to individual differences among patients, the degree of regulation of BCL11A gene on HbF has different effects in different patients. The BCL11A gene inhibits the expression of HbF, then editing the BCL11A erythroid enhancer to increase HbF to treat patients may fail, and if the patient has undergone chemotherapy to clear the bone marrow and immune system, this will cause unpredictable potential harm

Moreover, the mechanism for regulating the expression of γ-globin and HbF fetal hemoglobin is very complicated, and it is difficult to predict the effectiveness of treatment methods in advance by detecting the expression of a certain gene or several genes

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