Reference - Detail
| RRC ID | 86191 |
|---|---|
| Author | Yamato Y, Suzuki J. |
| Title | Phagocytic clearance of targeted cells with a synthetic ligand. |
| Journal | 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. |
| Published | 2025-9-3 |
| DOI | 10.1038/s41551-025-01483-9 |
| PII | 10.1038/s41551-025-01483-9 |
| PMID | 40903592 |
| IF | 18.952 |
| 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 | 54 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| DNA material | pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394) |