| 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
|
| Resource |
| Human and Animal Cells |
293T(RCB2202) |
| DNA material |
pCAG-HIVgp (RDB04394)
pCMV-VSV-G-RSV-Rev (RDB04393) |
