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Molecules 2018, 23(7), 1825; https://doi.org/10.3390/molecules23071825

Delivery of miRNA-Targeted Oligonucleotides in the Rat Striatum by Magnetofection with Neuromag®

1
Technology for Gene Therapy Laboratory, Central Institute of Sciences, FAV, University of Brasilia, Brasília 70910-900, Brazil
2
Neuroprosthetics and Visual Rehabilitation Research Unit, Bioengineering Institute, Miguel Hernández University, 03202 Alicante, Spain
3
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine—CIBER-BBN, 28029 Madrid, Spain
4
Biotechnology Department, University of Alicante, 03080 Alicante, Spain
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: T.J. Thomas
Received: 19 June 2018 / Revised: 17 July 2018 / Accepted: 21 July 2018 / Published: 23 July 2018
(This article belongs to the Special Issue Gene Delivery)
Full-Text   |   PDF [1819 KB, uploaded 23 July 2018]   |  

Abstract

MicroRNAs (miRNAs) regulate gene expression at posttranscriptional level by triggering RNA interference. In such a sense, aberrant expressions of miRNAs play critical roles in the pathogenesis of many disorders, including Parkinson’s disease (PD). Controlling the level of specific miRNAs in the brain is thus a promising therapeutic strategy for neuroprotection. A fundamental need for miRNA regulation (either replacing or inhibition) is a carrier capable of delivering oligonucleotides into brain cells. This study aimed to examine a polymeric magnetic particle, Neuromag®, for delivery of synthetic miRNA inhibitors in the rat central nervous system. We injected the miRNA inhibitor complexed with Neuromag® into the lateral ventricles next to the striatum, by stereotaxic surgery. Neuromag efficiently delivered oligonucleotides in the striatum and septum areas, as shown by microscopy imaging of fluorescein isothiocyanate (FITC)-labeled oligos in astrocytes and neurons. Transfected oligos showed efficacy concerning miRNA inhibition. Neuromag®-structured miR-134 antimiR (0.36 nmol) caused a significant 0.35 fold decrease of striatal miR-134, as revealed by real-time quantitative polymerase chain reaction (RT-qPCR). In conclusion, the polymeric magnetic particle Neuromag® efficiently delivered functional miRNA inhibitors in brain regions surrounding lateral ventricles, particularly the striatum. This delivery system holds potential as a promising miRNA-based disease-modifying drug and merits further pre-clinical studies using animal models of PD. View Full-Text
Keywords: miRNA; nanoparticles; Neuromag®; delivery miRNA; nanoparticles; Neuromag®; delivery
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Titze de Almeida, S.S.; Horst, C.H.; Soto-Sánchez, C.; Fernandez, E.; Titze de Almeida, R. Delivery of miRNA-Targeted Oligonucleotides in the Rat Striatum by Magnetofection with Neuromag®. Molecules 2018, 23, 1825.

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