論文 - 詳細
| RRC ID | 21519 |
|---|---|
| 著者 | Kaneko E, Kawahara M, Ueda H, Nagamune T. |
| タイトル | Growth control of genetically modified cells using an antibody/c-Kit chimera. |
| ジャーナル | J Biosci Bioeng |
| Abstract |
Gene therapy has been regarded as an innovative potential treatment against serious congenital diseases. However, applications of gene therapy remain limited, partly because its clinical success depends on therapeutic gene-transduced cells acquiring a proliferative advantage. To address this problem, we have developed the antigen-mediated genetically modified cell amplification (AMEGA) system, which uses chimeric receptors to enable the selective proliferation of gene-transduced cells. In this report, we describe mimicry of c-Kit signaling and its application to the AMEGA system. We created an antibody/c-Kit chimera in which the extracellular domain of c-Kit is replaced with an anti-fluorescein single-chain Fv antibody fragment and the extracellular D2 domain of the erythropoietin receptor. A genetically modified mouse pro-B cell line carrying this chimera showed selective expansion in the presence of fluorescein-conjugated BSA (BSA-FL) as a growth inducer. By further engineering the transmembrane domain of the chimera to reduce interchain interaction we attained stricter ligand-dependency. Since c-Kit is an important molecule in the expansion of hematopoietic stem cells (HSCs), this antibody/c-Kit chimera could be a promising tool for gene therapy targeting HSCs. |
| 巻・号 | 113(5) |
| ページ | 641-6 |
| 公開日 | 2012-5-1 |
| DOI | 10.1016/j.jbiosc.2011.12.005 |
| PII | S1389-1723(11)00520-2 |
| PMID | 22227120 |
| MeSH | Animals Antibodies / metabolism* Antigens / metabolism Cell Line Cell Proliferation Chimera / metabolism* Genetic Therapy Hematopoietic Stem Cells / cytology* Humans Mice Precursor Cells, B-Lymphoid Receptors, Erythropoietin / genetics Receptors, Erythropoietin / metabolism Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / immunology Recombinant Fusion Proteins / metabolism Signal Transduction Single-Chain Antibodies / genetics |
| IF | 2.366 |
| 引用数 | 17 |
| WOS 分野 | FOOD SCIENCE & TECHNOLOGY BIOTECHNOLOGY & APPLIED MICROBIOLOGY |
| 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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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 遺伝子材料 | pUC kit EH1 (RDB01344) |