Reference - Detail
| RRC ID | 77307 |
|---|---|
| Author | Li C, Wang H, Georgakopoulou A, Gil S, Yannaki E, Lieber A. |
| Title | In Vivo HSC Gene Therapy Using a Bi-modular HDAd5/35++ Vector Cures Sickle Cell Disease in a Mouse Model. |
| Journal | Mol Ther |
| Abstract |
We have recently reported that, after in vivo hematopoietic stem cell/progenitor (HSPC) transduction with HDAd5/35++ vectors, SB100x transposase-mediated γ-globin gene addition achieved 10%-15% γ-globin of adult mouse globin, resulting in significant but incomplete phenotypic correction in a thalassemia intermedia mouse model. Furthermore, genome editing of a γ-globin repressor binding site within the γ-globin promoter by CRISPR-Cas9 results in efficient reactivation of endogenous γ-globin. Here, we aimed to combine these two mechanisms to obtain curative levels of γ-globin after in vivo HSPC transduction. We generated a HDAd5/35++ adenovirus vector (HDAd-combo) containing both modules and tested it in vitro and after in vivo HSPC transduction in healthy CD46/β-YAC mice and in a sickle cell disease mouse model (CD46/Townes). Compared to HDAd vectors containing either the γ-globin addition or the CRISPR-Cas9 reactivation units alone, in vivo HSC transduction of CD46/Townes mice with the HDAd-combo resulted in significantly higher γ-globin in red blood cells, reaching 30% of that of adult human α and βS chains and a complete phenotypic correction of sickle cell disease. |
| Volume | 29(2) |
| Pages | 822-837 |
| Published | 2021-2-3 |
| DOI | 10.1016/j.ymthe.2020.09.001 |
| PII | S1525-0016(20)30458-5 |
| PMID | 32949495 |
| PMC | PMC7854285 |
| MeSH | Adenoviridae / genetics* Anemia, Sickle Cell / genetics* Anemia, Sickle Cell / therapy* Animals Disease Models, Animal Genetic Therapy* / methods Genetic Vectors / genetics* Hematopoietic Stem Cell Transplantation* / methods Hematopoietic Stem Cells / metabolism* Humans Mice Transgenes |
| IF | 8.986 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 17 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | HUDEP-2(RCB4557) |