Comparison of the expression and toxicity of AAV2/9 carrying the human A53T α-synuclein gene in presence or absence of WPRE

Xiuping Sun, Xuan Yu, Ling Zhang, Wenjie Zhao, Manshi Wang, Yu Zhang, Xianglei Li, Ran Gao, Ludivine S. Breger, Sandra Dovero, Gregory Porras, Pierre-Olivier Fernagut, Benjamin Dehay, Erwan Bezard, Chuan Qin
Heliyon. 2021-02-01; 7(2): e06302
DOI: 10.1016/j.heliyon.2021.e06302

Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) is thought to enhance transgeneexpression of target genes delivered by adeno-associated viral (AAV) vectors. This study assessed the proteinexpression ofα-synuclein, phosphorylatedα-synuclein at Serine 129, extent of nigrostriatal degeneration as wellas subsequent behavioral deficits induced by unilateral intranigral stereotactic injection in male adult C57BL/6Jmice of an AAV2/9 expressing A53T humanα-synuclein under the control of the synapsin promoter in presence orabsence of the WPRE. The presence of WPRE enabled to achieve greater nigrostriatal degeneration and synu-cleinopathy which was concomitant with worsened forelimb use asymmetry. This work refines a mouse Parkinson’s disease model in which anatomo-pathology is related to behavioral deficits.

Auteurs Bordeaux Neurocampus