Format

Send to

Choose Destination
  • Filters activated: Field: Title Word. Clear all
Mol Ther Nucleic Acids. 2017 Dec 15;9:57-68. doi: 10.1016/j.omtn.2017.08.013. Epub 2017 Aug 30.

Polyethylenimine Nanoparticle-Mediated siRNA Delivery to Reduce α-Synuclein Expression in a Model of Parkinson's Disease.

Author information

1
Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig 04103, Germany.
2
Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, Faculty of Medicine, University of Leipzig, Leipzig 04107, Germany.
3
Institute of Veterinary Pathology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig 04103, Germany.
4
Veterinary Institute of Anatomy, Histology, and Embryology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig 04103, Germany.
5
Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig 04103, Germany. Electronic address: angelika.richter@vetmed.uni-leipzig.de.

Abstract

RNA interference (RNAi)-based strategies that mediate the specific knockdown of target genes by administration of small interfering RNAs (siRNAs) could be applied for treatment of presently incurable neurodegenerative diseases such as Parkinson's disease. However, inefficient delivery of siRNA into neurons hampers in vivo application of RNAi. We have previously established the 4-12 kDa branched polyethylenimine (PEI) F25-LMW with superior transfection efficacy for delivery of siRNA in vivo. Here, we present that siRNA complexed with this PEI extensively distributes across the CNS down to the lumbar spinal cord after a single intracerebroventricular infusion. siRNA against α-synuclein (SNCA), a pre-synaptic protein that aggregates in Parkinson's disease, was complexed with PEI F25-LMW and injected into the lateral ventricle of mice overexpressing human wild-type SNCA (Thy1-aSyn mice). Five days after the single injection of 0.75 μg PEI/siRNA, SNCA mRNA expression in the striatum was reduced by 65%, accompanied by reduction of SNCA protein by ∼50%. Mice did not show signs of toxicity or adverse effects. Moreover, ependymocytes and brain parenchyma were completely preserved and free of immune cell invasion, astrogliosis, or microglial activation. Our results support the efficacy and safety of PEI nanoparticle-mediated delivery of siRNA to the brain for therapeutic intervention.

KEYWORDS:

Parkinson’s disease; RNA interference; intracerebroventricular; mouse model; nanoparticles; transfection; α-synuclein

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center