A brain-targeted rabies virus glycoprotein-disulfide linked PEI nanocarrier for delivery of neurogenic microRNA

Hwang, Do Won; Son, Sejin; Jang, Jae-Ho; Youn, Hyewon; Lee, Song; Lee, Duhwan; Lee, Yun Sang; Jeong, Jae Min; Kim, Won Jong; Lee, Dong Hoon

doi:10.1016/j.biomaterials.2011.03.047

Cited by 217 publications

(137 citation statements)

References 28 publications

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“…On the other side, nanotechnology studies of nanoparticle miRNA delivery are providing new strategies for the achievement of selected transcript brain distribution and modulation [213]. Recent data have shown that rabies virus glycoprotein (RGV)-labeled nanomaterials injected in mice resulted in neuron-specific miR-124a delivery in vivo [214].…”

Section: Future Treatment Direction: Mirnas As Potential Antipsychotimentioning

confidence: 99%

MicroRNAs in Schizophrenia: Implications for Synaptic Plasticity and Dopamine–Glutamate Interaction at the Postsynaptic Density. New Avenues for Antipsychotic Treatment Under a Theranostic Perspective

et al. 2014

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Despite dopamine-glutamate aberrant interaction that has long been considered a relevant landmark of psychosis pathophysiology, several aspects of these two neurotransmitters reciprocal interaction remain to be defined. The emerging role of postsynaptic density (PSD) proteins at glutamate synapse as a molecular "lego" making a functional hub where different signals converge may add a new piece of information to understand how dopamine-glutamate interaction may work with regard to schizophrenia pathophysiology and treatment. More recently, compelling evidence suggests a relevant role for microRNA (miRNA) as a new class of dopamine and glutamate modulators with regulatory functions in the reciprocal interaction of these two neurotransmitters. Here, we aimed at addressing the following issues: (i) Do miRNAs have a role in schizophrenia pathophysiology in the context of dopamine-glutamate aberrant interaction? (ii) If miRNAs are relevant for dopamine-glutamate interaction, at what level this modulation takes place? (iii) Finally, will this knowledge open the door to innovative diagnostic and therapeutic tools? The biogenesis of miRNAs and their role in synaptic plasticity with relevance to schizophrenia will be considered in the context of dopamine-glutamate interaction, with special focus on miRNA interaction with PSD elements. From this framework, implications both for biomarkers identification and potential innovative interventions will be considered.

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Section: Future Treatment Direction: Mirnas As Potential Antipsychotimentioning

confidence: 99%

MicroRNAs in Schizophrenia: Implications for Synaptic Plasticity and Dopamine–Glutamate Interaction at the Postsynaptic Density. New Avenues for Antipsychotic Treatment Under a Theranostic Perspective

et al. 2014

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“…The Rabies virus glycoprotein derived, RVG peptide is known to bind to the nicotinic acetylcholine receptor and has been used in combination with liposomes and nano-particles. The unique ability of this peptide to cross the blood brain barrier with minimal toxicity and carry siRNA, small molecules, anti-sense molecules or plasmid for delivery to the brain can be very useful in drug delivery to the CNS 8,15,16 . More specifically, a simple conjugate of the peptide with a modified anti-sense molecule, for CNS delivery of microRNA inhibitors by-passing the blood brain barrier can accelerate in vivo functional studies on neuronal miRNAs.…”

Section: Discussionmentioning

confidence: 99%

A Simple Alternative to Stereotactic Injection for Brain Specific Knockdown of miRNA

Suryawanshi

Sarangdhar

Vij

et al. 2015

JoVE

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MicroRNAs (miRNAs) are key regulators of gene expression. In the brain, vital processes like neurodevelopment and neuronal functions depend on the correct expression of microRNAs. Perturbation of microRNAs in the brain can be used to model neurodegenerative diseases by modulating neuronal cell death. Currently, stereotactic injection is used to deliver miRNA knockdown agents to specific location in the brain. Here, we discuss strategies to design antagomirs against miRNA with locked nucleotide modifications (LNA). Subsequently describe a method for brain specific delivery of antagomirs, uniformly across different regions of the brain. This method is simple and widely applicable since it overcomes the surgery, associated injury and limitation of local delivery in stereotactic injections. We prepared a complex of neurotropic, cellpenetrating peptide Rabies Virus Glycoprotein (RVG) with antagomir against miRNA-29 and injected through tail vein, to specifically deliver in the brain. The antagomir design incorporated features that allow specific targeting of the miRNA and formation of non-covalent complexes with the peptide. The knock-down of the miRNA in neuronal cells, resulted in apoptotic cell death and associated behavioural defects. Thus, the method can be used for acute models of neuro-degeneration through the perturbation of miRNAs. Video LinkThe video component of this article can be found at

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“…To this end, RVG linked to LSPCs (Pulford et al 2010) or to a disulfide polyethyleneimine (SSPEI) nanomaterial showed increased stability in the blood (Hwang et al 2011). Successful delivery of miR-124a to the brain was observed when complexes were injected into the blood, while a greater abundance transversed the BBB when mannitol was used to perfuse the brain (Hwang et al 2011). For all reported RVG-RNA complexes, the small RNA species delivered to the brain conferred functional activity through an unknown release mechanism.…”

Section: Microrna-based Therapeutics Targeting Neurodegenerative Disementioning

confidence: 96%

“…An alternative strategy would be to encapsulate siRNAs with liposomal nanoparticles shown to increase stability in serum (Leng et al 2009). To this end, RVG linked to LSPCs (Pulford et al 2010) or to a disulfide polyethyleneimine (SSPEI) nanomaterial showed increased stability in the blood (Hwang et al 2011). Successful delivery of miR-124a to the brain was observed when complexes were injected into the blood, while a greater abundance transversed the BBB when mannitol was used to perfuse the brain (Hwang et al 2011).…”

Section: Microrna-based Therapeutics Targeting Neurodegenerative Disementioning

confidence: 97%

The Role of MicroRNAs in Neurodegenerative Diseases: Implications for Early Detection and Treatment

Majer¹,

Boese²,

Booth

2011

Regulatory RNAs

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MicroRNAs (miRNAs) are small noncoding RNAs that can posttranscriptionally regulate gene expression in development, differentiation, and in response to various stimuli. Numerous miRNAs are very specifically expressed within the central nervous system suggesting they regulate important brain functions. MiRNAs are also required for the postmitotic survival of neurons, strongly suggesting a crucial role in survival and neuroprotection. The fact that diverse arrays of miRNAs have been reported to be dysregulated in several neurodegenerative diseases implies that they can contribute to pathogenesis. As a group, the global burden of neurodegenerative disease is huge and includes conditions such as Alzheimer's disease and other dementias, for which the numbers are steadily rising with the aging population, as well as communicable diseases caused by prions that are of public health concern. As yet, no drugs to halt or even delay the progression of these diseases are available, and this is a huge focus of global research. The best time for therapeutic intervention would be before significant memory loss and tissue destruction occurs such that interventions to boost cell repair and to promote neuroprotective mechanisms could provide significant health benefits. MicroRNA research promises to further elucidate the pathways, genes, and proteins that contribute to the neurodegenerative process that may serve as potential therapeutic targets. Furthermore, given the evidence of the neuroprotective properties of some miRNAs, these small RNA species may themselves be the focus for drug development. Here, we review recent studies that imply a link between miRNA function and neurodegeneration plus discuss how increased knowledge of miRNAs may be used in diagnosis and treatment of neurodegenerative diseases.

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A brain-targeted rabies virus glycoprotein-disulfide linked PEI nanocarrier for delivery of neurogenic microRNA

Cited by 217 publications

References 28 publications

MicroRNAs in Schizophrenia: Implications for Synaptic Plasticity and Dopamine–Glutamate Interaction at the Postsynaptic Density. New Avenues for Antipsychotic Treatment Under a Theranostic Perspective

MicroRNAs in Schizophrenia: Implications for Synaptic Plasticity and Dopamine–Glutamate Interaction at the Postsynaptic Density. New Avenues for Antipsychotic Treatment Under a Theranostic Perspective

A Simple Alternative to Stereotactic Injection for Brain Specific Knockdown of miRNA

The Role of MicroRNAs in Neurodegenerative Diseases: Implications for Early Detection and Treatment

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