Nature Medicine of East China Normal University reports the world's first clinical results of CRISPR gene editing in children with β0/β0 severe thalassaemia

Beta-thalassemia is an inherited hemolytic disease that is prevalent worldwide and is one of the most common monogenic diseases 1

Recently, the team of Wu Yuxuan, Liu Mingyao, and Li Dali from the School of Life Sciences of East China Normal University, Fu Bin's team from Xiangya Hospital of Central South University, and Bangyao Biology jointly published a paper entitled CRISPR–Cas9-mediated gene editing of the BCL11A enhancer in the journal Nature Medicine.

Disruption of the GATA1 binding site of the +58 BCL11A erythroid enhancer by gene editing induces γ-globin expression, a promising therapeutic strategy for alleviating β-hemoglobinopathies caused by mutations in the HBB gene 5-7

The trial transplanted gene-edited autologous hematopoietic stem progenitor cells (HSPCs) into two pediatric patients, one with the β0/β0 genotype classified as the most severe type of TDT; the other treated with Also belongs to TDT

Changes of red blood cells and hemoglobin after transplantation, the proportion of F cells and iron metabolism data

Exploratory analysis of the indel patterns in the edited PBMCs revealed that no abnormal clonal expansion was observed during the nearly two-year follow-up period

Expression of B-cell proliferation-related genes in B-cell clusters from healthy donors and gene-edited patients

In conclusion, this study provides proof-of-principle that engraftment and long-term engraftment of CRISPR/Cas9-edited autologous HSPCs can be achieved, and confirms that sustained elevation of fetal hemoglobin levels is sufficient to ameliorate transfusion-dependent β-thalassemia, even for β-beads.

Professor Wu Yuxuan, Professor Liu Mingyao and Professor Li Dali are the co-corresponding authors of the paper

references

1 Piel, FB The present and future global burden of the inherited disorders of hemoglobin.

2 Yin, XL et al.

3 Modell, B.

4 Li, C.

5 Wu, Y.

6 Wang, L.

7 Demirci, S.

Full text link:

https://doi.
org/10.
1038/s41591-022-01906-z