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

Simoneide Titze De Almeida,Camila Horst,Ricardo Titze De Almeida,Cristina Soto-Sánchez,Eduardo Fernandez

doi:10.3390/molecules23071825

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.

Highlights

MicroRNAs are endogenous short noncoding RNAs that cause post-transcriptional gene silencing in healthy cells
Exogenous synthetic oligonucleotides have been used to modulate the content of specific
We examined whether NeuroMag® -complexed miR-134 inhibitors injected by the i.c.v

Summary

Introduction

MicroRNAs (miRNAs) are endogenous short noncoding RNAs that cause post-transcriptional gene silencing in healthy cells. Knocking down first requires the binding of miRNA guide strands, complexed with silencing proteins, to complementary sequences in 30 -untranslated region (30 -UTR). Of the target mRNAs. of the target mRNAs This silencing complex will cause translational repression or mRNA degradation [1]. RNAi is a crucial mechanism of gene regulation. Aberrant expressions of miRNAs play critical roles in the neuropathology of brain diseases [2]. Exogenous synthetic oligonucleotides have been used to modulate the content of specific

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