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      Magnetic nanoparticles loaded with functional RNA nanoparticles

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          Abstract

          RNA nanoparticle constructs complexed with polyethylenimine-coated iron oxide nanoparticles are protected from enzymatic degradation and knockdown is amplified by magnetic stimulus in mammalian cells.

          Abstract

          RNA is now widely acknowledged not only as a multifunctional biopolymer but also as a dynamic material for constructing nanostructures with various biological functions. Programmable RNA nanoparticles (NPs) allow precise control over their formulation and activation of multiple functionalities, with the potential to self-assemble in biological systems. These attributes make them attractive for drug delivery and therapeutic applications. In the present study, we demonstrate the ability of iron oxide magnetic nanoparticles (MNPs) to deliver different types of RNA NPs functionalized with dicer substrate RNAs inside human cells. Our results show that use of functionalized RNA NPs result in statistically higher transfection efficiency compared to the use of RNA duplexes. Furthermore, we show that the nucleic acids in the MNP/RNA NP complexes are protected from nuclease degradation and that they can achieve knockdown of target protein expression, which is amplified by magnetic stimulus. The current work represents the very first report indicating that iron oxide nanoparticles may efficiently protect and deliver programmable RNA NPs to human cells.

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          Most cited references37

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          Is Open Access

          Advances in the delivery of RNA therapeutics: from concept to clinical reality

          The rapid expansion of the available genomic data continues to greatly impact biomedical science and medicine. Fulfilling the clinical potential of genetic discoveries requires the development of therapeutics that can specifically modulate the expression of disease-relevant genes. RNA-based drugs, including short interfering RNAs and antisense oligonucleotides, are particularly promising examples of this newer class of biologics. For over two decades, researchers have been trying to overcome major challenges for utilizing such RNAs in a therapeutic context, including intracellular delivery, stability, and immune response activation. This research is finally beginning to bear fruit as the first RNA drugs gain FDA approval and more advance to the final phases of clinical trials. Furthermore, the recent advent of CRISPR, an RNA-guided gene-editing technology, as well as new strides in the delivery of messenger RNA transcribed in vitro, have triggered a major expansion of the RNA-therapeutics field. In this review, we discuss the challenges for clinical translation of RNA-based therapeutics, with an emphasis on recent advances in delivery technologies, and present an overview of the applications of RNA-based drugs for modulation of gene/protein expression and genome editing that are currently being investigated both in the laboratory as well as in the clinic.
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            A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine.

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              Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo.

              Low efficiencies of nonviral gene vectors, the receptor-dependent host tropism of adenoviral or low titers of retroviral vectors limit their utility in gene therapy. To overcome these deficiencies, we associated gene vectors with superparamagnetic nanoparticles and targeted gene delivery by application of a magnetic field. This potentiated the efficacy of any vector up to several hundred-fold, allowed reduction of the duration of gene delivery to minutes, extended the host tropism of adenoviral vectors to nonpermissive cells and compensated for low retroviral titer. More importantly, the high transduction efficiency observed in vitro was reproduced in vivo with magnetic field-guided local transfection in the gastrointestinal tract and in blood vessels. Magnetofection provides a novel tool for high throughput gene screening in vitro and can help to overcome fundamental limitations to gene therapy in vivo.
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                Author and article information

                Contributors
                (View ORCID Profile)
                (View ORCID Profile)
                Journal
                NANOHL
                Nanoscale
                Nanoscale
                Royal Society of Chemistry (RSC)
                2040-3364
                2040-3372
                2018
                2018
                : 10
                : 37
                : 17761-17770
                Affiliations
                [1 ]J. Crayton Pruitt Family Department of Biomedical Engineering
                [2 ]University of Florida
                [3 ]Gainesville
                [4 ]USA
                [5 ]Department of Chemistry
                [6 ]University of North Carolina at Charlotte
                [7 ]Charlotte
                [8 ]Department of Materials Science and Engineering
                [9 ]Department of Chemical Engineering
                Article
                10.1039/C8NR04254C
                dc1dad68-3cc0-4f90-bc3a-7ca14a5320d9
                © 2018

                Free to read

                http://rsc.li/journals-terms-of-use#chorus

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