論文 - 詳細
| RRC ID | 86002 |
|---|---|
| 著者 | Chu SN, Soupene E, Sharma D, Sinha R, McCreary T, Hernandez B, Shen H, Wienert B, Bowman C, Yin H, Lesch BJ, Jia K, Romero KA, Kostamo Z, Zhang Y, Tran T, Cordero M, Homma S, Hampton JP, Gardner JM, Conklin BR, MacKenzie TC, Sheehan VA, Porteus MH, Cromer MK. |
| タイトル | Dual α-globin-truncated erythropoietin receptor knockin restores hemoglobin production in α-thalassemia-derived erythroid cells. |
| ジャーナル | Cell Rep |
| Abstract |
The most severe form of α-thalassemia results from loss of all four copies of α-globin. Postnatally, patients face challenges similar to β-thalassemia, including severe anemia and erythrotoxicity due to the imbalance of β-globin and α-globin chains. Despite progress in genome editing treatments for β-thalassemia, there is no analogous curative option for α-thalassemia. To address this, we designed a Cas9/AAV6-mediated genome editing strategy that integrates a functional α-globin gene into the β-globin locus in α-thalassemia patient-derived hematopoietic stem and progenitor cells (HSPCs). Incorporation of a truncated erythropoietin receptor transgene into the α-globin integration cassette significantly increased erythropoietic output from edited HSPCs and led to the most robust production of α-globin, and consequently hemoglobin tetramers. By directing edited HSPCs toward increased production of clinically relevant erythroid cells, this approach has the potential to mitigate the limitations of current treatments for the hemoglobinopathies, including low genome editing and low engraftment rates. |
| 巻・号 | 44(1) |
| ページ | 115141 |
| 公開日 | 2025-1-28 |
| DOI | 10.1016/j.celrep.2024.115141 |
| PII | S2211-1247(24)01492-X |
| PMID | 39754719 |
| PMC | PMC11837859 |
| MeSH | CRISPR-Cas Systems Erythroid Cells* / metabolism Erythropoiesis Gene Editing Gene Knock-In Techniques Hematopoietic Stem Cells / metabolism Hemoglobins* / biosynthesis Hemoglobins* / metabolism Humans Receptors, Erythropoietin* / genetics Receptors, Erythropoietin* / metabolism alpha-Globins* / genetics alpha-Globins* / metabolism alpha-Thalassemia* / genetics alpha-Thalassemia* / metabolism alpha-Thalassemia* / pathology beta-Globins / genetics beta-Globins / metabolism |
| IF | 8.109 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 13 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HUDEP-2(RCB4557) |