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

Springer Science and Business Media LLC - Tập 23 Số 7 - Trang 1825
Simoneide Souza Titze-de-Almeida1, Camila Hillesheim Horst1, Cristina Soto-Sánchez2,3,4, Eduardo Fernández2,4, Ricardo Titze‐de‐Almeida1
1Technology for Gene Therapy Laboratory, Central Institute of Sciences, FAV, University of Brasilia, Brasília 70910-900, Brazil
2Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine—CIBER-BBN, 28029 Madrid, Spain
3Biotechnology Department, University of Alicante, 03080 Alicante, Spain
4Neuroprosthetics and Visual Rehabilitation Research Unit, Bioengineering Institute, Miguel Hernández University, 03202 Alicante, Spain

Tóm tắt

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.

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Springer Science and Business Media LLC

Tập 23 Số 7

1825

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