CRISPR-mediated gene modification of hematopoietic stem cells with beta-thalassemia IVS-1-110 mutation.
PMID 32912325 | PMCID PMC7488347 | DOI 10.1186/s13287-020-01876-4 · Stem cell research & therapy · 2020
BACKGROUND: β-Thalassemias represent a group of genetic disorders caused by human hemoglobin beta (HBB) gene mutations. The radical curative approach is to correct the mutations causing the disease. CRISPR-CAS9 is a novel gene-editing technology that can be used auspiciously for the treatment of these disorders. The study aimed to investigate the utility of CRISPR-CAS9 for gene modification of hematopoietic stem cells in β-thalassemia with IVS-1-110 mutation. METHODS AND RESULTS: We successfully isolated CD34+ cells from peripheral blood of β-thalassemia patients with IVS-1-110 mutation. The cells were transfected with Cas9 endonuclease together with guide RNA to create double-strand breaks and knock out the mutation. The mutation-corrected CD34+ cells were subjected to erythroid differentiation by culturing in complete media containing erythropoietin. CONCLUSION: CRISPR/Cas-9 is an effective tool for gene therapy that will broaden the spectrum of therapy and potentially improve the outcomes of β-thalassemia.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | HBB | “BACKGROUND: β-Thalassemias represent a group of genetic disorders caused by human hemoglobin beta (HBB) gene mutations.” | 0.98 | hgnc_dict_v1 |
| gene | CD34 | “METHODS AND RESULTS: We successfully isolated CD34+ cells from peripheral blood of β-thalassemia patients with IVS-1-110 mutation.” | 0.98 | hgnc_dict_v1 |
| phenotype | thalassemia | “CRISPR-mediated gene modification of hematopoietic stem cells with beta-thalassemia IVS-1-110 mutation.” | 0.93 | phenotype_alias_lexicon_v2 |
| variant | IVS-1-110 | “CRISPR-mediated gene modification of hematopoietic stem cells with beta-thalassemia IVS-1-110 mutation.” | 0.82 | literature_variant_regex_v2 |