Reference - Detail
| RRC ID | 88187 |
|---|---|
| Author | Ono H, Fujino S, Sunagawa GA. |
| Title | Computationally guided discovery of Ly6e/LY6E-dependent AAV capsid variants. |
| Journal | 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. |
| Volume | 29(5) |
| Pages | 115554 |
| Published | 2026-5-15 |
| DOI | 10.1016/j.isci.2026.115554 |
| PII | S2589-0042(26)00929-6 |
| PMID | 42028008 |
| PMC | PMC13101293 |
| IF | 4.447 |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | X(Twitter) |
| Total number of mentions | 10 |
| Altmetric score changes over past 6months | 5.9 |
| Resource | |
| Human and Animal Cells | 293T(RCB2202) |
| DNA material | pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) |