Novel disease-specific promoters for use in gene therapy for Parkinson's disease

Gene therapy is a promising therapeutic tool for Parkinson's disease (PD), but there is a lack of evaluated cell specific promoters that are relevant for the disease. We have chosen PD relevant promoter candidates for gene therapy vectors based on either previous studies; Drd1a, Drd2 and pDyn, or from a microarray study on parkinsonian patients; ACE, DNAJC3, GALNS, MAP1a and RNF25. These candidates have been evaluated in rat striatum to determine their suitability for use in cell specific vectors. The promoters had a neuronal specificity of 91–100%. The efficiency of the promoters was variable, but RNF25, DNAJC3 and MAP1a were comparable to widely used ubiquitous promoters. MAP1a was also affected by dopamine depletion.

► We show two approaches for finding Parkinson's disease relevant promoters.
► The promoters are evaluated using lentiviral vectors in rat striatum.
► The promoters have similar specificity and efficiency as conventional promoters.
► The MAP1a promoter is also affected by dopamine depletion.