rAAV9-shRNA JDP

rAAV9-shRNA JDP is a preclinical gene therapy construct designed to knock down the expression of endogenous J-domain proteins (JDPs) using short hairpin RNA (shRNA) delivered via a recombinant adeno-associated virus serotype 9 (rAAV9) vector. JDPs are molecular chaperones that play a critical role in protein quality control, specifically in preventing the aggregation and seeding of misfolded tau proteins associated with tauopathies like Alzheimer's disease. In research conducted at the University of Texas Southwestern Medical Center, this construct was used to evaluate the impact of JDP loss-of-function on tau pathology in the PS19 mouse model. While JDP overexpression showed therapeutic potential by reducing tau seeding, the shRNA-mediated reduction of endogenous JDPs was used to investigate whether decreased chaperone activity exacerbates disease progression.