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Title: | Recombinant pre-miR-29b for Alzheimer´s disease therapeutics | Authors: | Pereira, Patrícia A Tomás, Joana F Queiroz, João A Figueiras, Ana R. Sousa, Fani |
Issue Date: | 28-Jan-2016 | Publisher: | Springer Nature | metadata.degois.publication.title: | Scientific Reports | metadata.degois.publication.volume: | 6 | metadata.degois.publication.issue: | 1 | Abstract: | MicroRNAs are arising as the next generation of diagnostic and therapeutic tools for gene silencing. Studies demonstrated that the miR-29 expression is decreased in Alzheimer's disease (AD) patients displaying high levels of human β-secretase (hBACE1). Recent advances toward an effective therapy for AD intend to employ miR-29 to suppress hBACE1 expression and subsequent Amyloid-β (Aβ) peptide. However, delivery of mature miRNA has demonstrated modest efficacy in vitro; therefore, the preparation of highly pure and biologically active pre-miRNA arises as one of the most important challenges in the development of these therapeutic strategies. Recently, we described a new strategy based arginine-affinity chromatography to specifically purify the recombinant pre-miR-29b. Following this strategy, the purified pre-miR-29b was successfully encapsulated into polyplexes that were further delivered in cytoplasm. It was verified that Chitosan/pre-miR-29b and Polyethylenimine/pre-miR-29b systems efficiently delivered pre-miR-29b to N2a695 cells, thus reducing the hBACE1 protein expression (around 78% and 86%, respectively) and Aβ42 levels (approximately 44% and 47%, respectively). Furthermore, pre-miR-29b downregulates the hBACE1 mRNA expression in 80%. Overall, it was demonstrated that the recombinant pre-miR-29b using polyplexes allowed to decrease the hBACE1 and Aβ42 expression levels, improving the currently available methodologies of miRNA-based therapeutics. | URI: | https://hdl.handle.net/10316/108900 | ISSN: | 2045-2322 | DOI: | 10.1038/srep19946 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
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Recombinant-premiR29b-for-Alzheimers-disease-therapeuticsScientific-Reports.pdf | 2.73 MB | Adobe PDF | View/Open |
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