What they found
Low-intensity focused ultrasound (FUS) combined with IV microbubbles achieved non-invasive, spatially precise AAV9 delivery to the macaque cerebellum by transiently opening the blood-brain barrier. ssAAV9-CMV-mCherry achieved robust transduction of virtually all neurons in the targeted deep cerebellar nuclei. Two vector types were tested (scAAV9-CBA-GFP and ssAAV9-CMV-mCherry), both with high spatial precision. This is among the first demonstrations of FUS-mediated AAV gene therapy in NHP deep brain structures.
Lateral connection
The cochlea has analogous barrier challenges: the blood-labyrinth barrier limits systemic delivery of gene therapy vectors. FUS-mediated transient barrier opening could enable non-invasive cochlear gene delivery without surgical round window injection. The NHP success with AAV9 is relevant because AAV serotypes with inner ear tropism (Anc80L65, AAV9) could potentially be delivered systemically with FUS targeting the cochlea. This would eliminate the surgical delivery bottleneck that currently limits all inner ear gene therapies.
Hypothesis suggested
FUS + IV microbubbles could enable non-invasive cochlear gene delivery by transiently opening the blood-labyrinth barrier, allowing systemically administered AAV or LNP vectors to transduce hair cells. Maps to Alternative STRC Delivery Hypotheses (reference tier) and indirectly supports STRC Mini-STRC Single-Vector (S-tier) and STRC mRNA-LNP Strategy B (S-tier) by expanding delivery options. Testable: does FUS targeting the cochlea in a rodent model open the blood-labyrinth barrier sufficiently for AAV9 transduction of OHCs?
What could be computed
Acoustic simulation of FUS focal zone size achievable in the temporal bone at cochlear depth. Comparison of blood-labyrinth barrier vs. BBB permeability thresholds for AAV9 passage. Literature meta-analysis of FUS parameters (frequency, pressure, microbubble dose) that achieved barrier opening without tissue damage.
Links
Connections
[source]auto-indexed 2026-04-21 by strc-lit-watch