論文 - 詳細
| RRC ID | 88187 |
|---|---|
| 著者 | Ono H, Fujino S, Sunagawa GA. |
| タイトル | Computationally guided discovery of Ly6e/LY6E-dependent AAV capsid variants. |
| ジャーナル | iScience |
| Abstract |
Systemic adeno-associated virus (AAV) delivery to the central nervous system (CNS) would broaden neuroscience studies and therapeutic development, but capsids evolved in mice often underperform across species. We used structure-guided computational prioritization of short peptide inserts predicted to engage the BBB-associated Ly6-family receptor Ly6e/LY6E, grafting candidates into a surface loop of an AAV9 capsid. Selected variants increased blood-brain barrier transduction and enabled widespread CNS gene delivery in Syrian hamsters after intravenous dosing, with lead capsids showing Ly6e-dependent binding and transduction in cell assays. Using the same strategy for the human ortholog, we identified multiple AAV9 variants with LY6E-dependent enhancement of in vitro transduction. These capsids support species-matched CNS delivery and demonstrate how receptor-informed computation can focus experimental screening when in vivo library selection is impractical. |
| 巻・号 | 29(5) |
| ページ | 115554 |
| 公開日 | 2026-5-15 |
| DOI | 10.1016/j.isci.2026.115554 |
| PII | S2589-0042(26)00929-6 |
| PMID | 42028008 |
| PMC | PMC13101293 |
| IF | 4.447 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 10 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 5.9 |
| リソース情報 | |
| ヒト・動物細胞 | 293T(RCB2202) |
| 遺伝子材料 | pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) |