Systemic delivery of messenger RNA for the treatment of pancreatic cancer using polyplex nanomicelles with a cholesterol moiety

Uchida, Satoshi; Kinoh, Hiroaki; Ishii, Takehiko; Matsui, Aya; Tockary, Theofilus A.; Takeda, Kaori M.; Uchida, Hirokuni; Osada, Kensuke; Itaka, Keiji; Kataoka, Kazunori

doi:10.1016/j.biomaterials.2015.12.031

Cited by 133 publications

(89 citation statements)

References 36 publications

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“…In recent decades, nanoparticle-mediated delivery of biomolecules has received much attention for its potential to modulate the regulation of gene expression for the treatment of diseases, thus representing a promising new avenue for gene therapy [97,98,99,100]. The advantages of non-viral gene delivery systems compared to viral systems are clear in terms of the immunogenic responses.…”

Section: Delivery Methodsmentioning

confidence: 99%

Targeting Splicing in the Treatment of Human Disease

Suñé-Pou

Prieto-Sánchez

Boyero-Corral

et al. 2017

Genes

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The tightly regulated process of precursor messenger RNA (pre-mRNA) alternative splicing (AS) is a key mechanism in the regulation of gene expression. Defects in this regulatory process affect cellular functions and are the cause of many human diseases. Recent advances in our understanding of splicing regulation have led to the development of new tools for manipulating splicing for therapeutic purposes. Several tools, including antisense oligonucleotides and trans-splicing, have been developed to target and alter splicing to correct misregulated gene expression or to modulate transcript isoform levels. At present, deregulated AS is recognized as an important area for therapeutic intervention. Here, we summarize the major hallmarks of the splicing process, the clinical implications that arise from alterations in this process, and the current tools that can be used to deliver, target, and correct deficiencies of this key pre-mRNA processing event.

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Section: Delivery Methodsmentioning

confidence: 99%

Targeting Splicing in the Treatment of Human Disease

Suñé-Pou

Prieto-Sánchez

Boyero-Corral

et al. 2017

Genes

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“…In a recent study, soluble fms-like tyrosine kinase 1 (sFlt-1), an anti-angiogenic protein, was efficiently expressed in a pancreatic tumor-bearing mouse model after intravenous injection of mRNA encoding sFlt-1 encapsulated in a nanomicelle system stabilized by cholesterol. Using this mRNA-based nanomedicine for systemic anti-angiogenic therapy, a remarkable anti-cancer effect was observed for the first time in an intractable pancreatic cancer model [171]. …”

Section: Biomedical Applicationsmentioning

confidence: 99%

Biomedical applications of mRNA nanomedicine

et al. 2018

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As an attractive alternative to plasmid DNA, messenger RNA (mRNA) has recently emerged as a promising class of nucleic acid therapeutics for biomedical applications. Advances in addressing the inherent shortcomings of mRNA and in the development of nanoparticle-based delivery systems have prompted the development and clinical translation of mRNA-based medicines. In this review, we discuss the chemical modification strategies of mRNA to improve its stability, minimize immune responses, and enhance translational efficacy. We also highlight recent progress in nanoparticle-based mRNA delivery. Considerable attention is given to the increasingly widespread applications of mRNA nanomedicine in the biomedical fields of vaccination, protein-replacement therapy, gene editing, and cellular reprogramming and engineering.

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“…The core (laur) PEG polymer consists of a core of lauroyl ester of mucic acid (19,000 Da) and a shell of mPEG-5000. The unimolecular micelles formed had a mean diameter of 50 nm 26 .…”

Section: Uni-molecular Micellementioning

confidence: 99%

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2018

IJPSR

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ABSTRACT:In this article, we have reviewed several features of nanomicelles relating to their general properties, preparation and characterization techniques, and their applications in the areas of ocular drug delivery system. Nanomicelles can be rummage-sale as 'smart drug carriers' for targeting certain areas of the eye by making them stimuli-sensitive or by attachment of a specific ligand molecule onto their surface. In present scenario, the major challenge for the researchers is ocular drug delivery system as eye is the most sensitive organ in our body. Topical eye drop is the best suited way for delivery of drugs for the treatment of anterior segment of the eye. Delivery of the drugs to the targeted areas is restricted by the various barriers and even the amount instilled do not remain there for a long duration of time. In the past many years scientist are working on providing the masses the way for delivering drug in a novel, safe and patience compliance manner. The aided the basic delivery by providing the administration through various permeation enhancers and viscosity modifiers. Widely studied subjects in nanoscience technology is related to the conception of supramolecular architectures with well-defined structures and functionalities. Nanomicelles have congregated considerable attention in the field of drug and ocular drug delivery due to their exceptional biocompatibility, low toxicity, enhanced blood circulation time.

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Systemic delivery of messenger RNA for the treatment of pancreatic cancer using polyplex nanomicelles with a cholesterol moiety

Cited by 133 publications

References 36 publications

Targeting Splicing in the Treatment of Human Disease

Targeting Splicing in the Treatment of Human Disease

Biomedical applications of mRNA nanomedicine

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