Regulation of human GDNF gene expression in nigral dopaminergic neurons using a new doxycycline-regulated NTS-polyplex nanoparticle system

We constructed NTS-polyplex nanoparticles containing a single bifunctional plasmid that codes for the reverse tetracycline-controlled transactivator advanced under the control of NBRE3x promoter, and for hGDNF under the control of tetracycline-response element. Those NPs were injected into the rat substantia nigra. Accordingly, doxycycline administration activated hGDNF expression only in transfected dopaminergic neurons, whereas doxycycline withdrawal silenced transgene expression. Our results offer a specific regulatable system free of hGDNF transcriptional leakage for use in gene therapy for Parkinson's disease.295