Although gene therapy targeting the α-synuclein gene (SNCA) has achieved outstanding results in the treatment of Parkinson's disease (PD), the lack of a suitable gene delivery system and inadequate therapeutic effects remains a tremendous obstacle for RNAi therapy. Here, a degradable nano-MgO micelle composite (MgO(pDNA)-INS-Plu-mRNA-NGF) with double interference (mediated by RNAi and α-synuclein (α-syn)-targeted mRNA) was constructed. Binding mRNA treatment significantly increased the inhibitory effect compared to the reduction of α-syn expression by RNAi alone. Moreover, the cell experiments demonstrated that the viability of the PD cell model can be significantly improved by nano-MgO micelle composite treatment. More importantly, the composite has the ability to penetrate the blood brain barrier and deliver genes and mRNA to neurons through endocytosis mediated by the nerve growth factor and its receptors, thus significantly downregulating the expression of α-syn in the PD mice model without causing damage to other major organs. Overall, this work provides a novel insight into the design of biomaterials for gene therapy for PD.
Keywords: Parkinson’s disease; double interfering; gene therapy; nanomagnesia.