Dent disease gene therapy: lasting expression does not guarantee kidney benefit in mice
Published in Biology, Drugs development & discovery, Journals.
Published November 3, 2026.
A mouse study of Dent disease type 1 shows why persistent gene expression alone is an incomplete measure of gene-therapy success. Researchers at Wake Forest compared renal delivery of human CLCN5 using lentiviral and AAV9 vectors.
In mutant adult mice, combining lentiviral delivery with locally administered rapamycin-loaded biodegradable microspheres improved ClC-5 expression and reduced urinary β2-microglobulin for up to ten months.
AAV9 produced a different picture. Treatment in newborn mice temporarily reduced urinary protein markers despite continued ClC-5 expression. In adults, expression persisted for eight to ten months without consistent improvement in urinary β2-microglobulin, including with rapamycin.
The findings highlight vector choice, treatment age and delivery to the relevant kidney cells as important design considerations. They do not demonstrate a cure, consistent correction of calcium excretion, or clinical safety and effectiveness in humans.
Source: Pin Lyu, Aykut Bostanci, Cuili Jiang and colleagues, Gene Therapy, original study published November 2, 2026. Wake Forest Baptist Medical Center has filed a related patent.