BIOBRIEFPAPER
An engineered virus called ShH10Y445F — a variant of the gene therapy vector AAV6 — reaches the brain's CSF producing choroid plexus in mouse, rat, and pig tissue, but a single injection leaves the third and fourth ventricles under edited, with
Engineered from AAV6, the capsid ShH10Y445F was tested on mouse, rat, and pig tissue explants and in live mice. The vectors carried either a GFP reporter or a CRISPR/Cas9 system (SaCas9) targeting aquaporin-1, a water channel that sits in the choroid plexus, the lining that produces cerebrospinal fluid.
The vector finds the right cell type. After a single unilateral intracerebroventricular injection, however, transduction concentrated in the choroid plexus of the lateral ventricle on the injected side. The third and fourth ventricles were far less covered, a pattern the authors themselves name as the central clinical-translation hurdle for any whole-CP gene therapy.
The work is preclinical: in vivo data comes only from mice, and the broader cross-species result rests on ex vivo explant cultures. Quantitative immunofluorescence and a SURVEYOR assay tracked both the spread and the knockdown of aquaporin-1 across the ventricular system.
What remains unknown is whether multiple injections, different infusion routes, or further capsid engineering can close the lateral-to-medial coverage gap. The paper appeared in Fluids and Barriers of the CNS in 2026 (PMID 42538560).