Structural basis of liver de-targeting and neuronal tropism of CNS-targeted AAV capsids - PubMed
3 hours ago
- #gene therapy
- #structural biology
- #AAV capsids
- Engineered capsid PHP.eB enhances brain transduction in mice.
- Further engineered CAP-B10 is de-targeted from astrocytes and liver.
- Cryo-EM structures of CAP-B10 and its complex with AAVR domain PKD2 reveal a motif hindering AAVR binding.
- This motif is transferable to other capsids, as shown by cryo-EM structures of AAV9-X1 variants.
- Novel AAV variants were designed and validated in vivo with reduced liver tropism and altered brain cell targeting.
- Provides a structural framework for rational engineering of safe and effective gene delivery vectors.