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.
CNS Gene Therapy Unit, BMC A11, Dept. of Experimental Medical Science, Lund University, S-221 84 Lund, Sweden.
Erika Elgstrand
EE
Wettergren
Fredrik
F
Gussing
Luis
L
Quintino
Cecilia
C
Lundberg
D000818:Animals; D002811:Chondroitinsulfatases / Q000235:genetics; D003342:Corpus Striatum / Q000502:physiology; D004298:Dopamine / Q000172:deficiency; D059290:Dopaminergic Neurons / Q000502:physiology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010300:Parkinson Disease / Q000235:genetics* / Q000628:therapy*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
C494651:DNAJC3 protein, human; D050956:HSP40 Heat-Shock Proteins; C093429:MAP1A protein, human; D008869:Microtubule-Associated Proteins; C476616:RNF25 protein, human; D044767:Ubiquitin-Protein Ligases; D002811:Chondroitinsulfatases; C102295:GALNS protein, human; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A; D004298:Dopamine