論文 - 詳細
| RRC ID | 86191 |
|---|---|
| 著者 | Yamato Y, Suzuki J. |
| タイトル | Phagocytic clearance of targeted cells with a synthetic ligand. |
| ジャーナル | Nat Biomed Eng |
| Abstract |
During the process of engulfment, phosphatidylserine is exposed on the surface of dead cells as an 'eat-me' signal and is recognized by Protein S (ProS), a secreted factor that also binds to the Mer tyrosine kinase (MerTK) on phagocytes. Despite its robust activity, this engulfment mechanism has not been exploited for therapeutic purposes. Here we develop a synthetic protein modality called Crunch (connector for removal of unwanted cell habitat) by modifying ProS, inspired by the high engulfment capability of the ProS-MerTK pathway. In Crunch, the phosphatidylserine-binding motif of ProS is replaced with a nanobody or single-chain variable fragment that recognizes the surface proteins of targeted cells. Green fluorescent protein nanobody-conjugated Crunch eliminates green fluorescent protein-expressing melanoma cells in transplantation mouse models. In addition, CD19+B cells are eliminated by anti-CD19 single-chain variable fragment-conjugated Crunch, resulting in a therapeutic effect on systemic lupus erythematosus. Both mouse and human versions of Crunch are effective, establishing this synthetic ligand as a promising tool for the elimination of targeted cells. |
| 公開日 | 2025-9-3 |
| DOI | 10.1038/s41551-025-01483-9 |
| PII | 10.1038/s41551-025-01483-9 |
| PMID | 40903592 |
| IF | 18.952 |
| 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 | 54 |
| 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 | |
| 遺伝子材料 | pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394) |