Nanoparticle-based local translation reveals mRNA as a translation-coupled scaffold with anchoring function

Kashida, Shunnichi; Wang, Dan Ohtan; Saito, Hirohide; Gueroui, Zoher

doi:10.1073/pnas.1900310116

Cited by 4 publications

(3 citation statements)

References 51 publications

(44 reference statements)

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“…mRNA drugs have emerged as a safe and efficacious strategy for protecting patients from infectious diseases and cancers owing to their advantages, including high efficiency, low side efficacy, and ease of manufacture. mRNAs display high therapeutic efficacy due to their continuous translation into encoded proteins/peptides compared to transient traditional protein/peptide drugs [69]. mRNA has been successfully transfected and produced an immune response in a dose-dependent manner [70].…”

Section: Mrna Vaccines As Anti-cancer Therapeuticsmentioning

confidence: 99%

Cancer/Testis Antigens as Targets for RNA-Based Anticancer Therapy

Shim,

Jo,

Jeoung

2023

IJMS

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In the last few decades, RNA-based drugs have emerged as a promising candidate in the treatment of various diseases. The introduction of messenger RNA (mRNA) as a vaccine or therapeutic agent enables the production of almost any functional protein/peptide. The key to applying RNA therapy in clinical trials is developing safe and effective delivery systems. Exosomes and lipid nanoparticles (LNPs) have been exploited as promising vehicles for drug delivery. This review discusses the feasibility of exosomes and LNPs as vehicles for mRNA delivery. Cancer/testis antigens (CTAs) show restricted expression in normal tissues and widespread expression in cancer tissues. Many of these CTAs show expression in the sera of patients with cancers. These characteristics of CTAs make them excellent targets for cancer immunotherapy. This review summarizes the roles of CTAs in various life processes and current studies on mRNAs encoding CTAs. Clinical studies present the beneficial effects of mRNAs encoding CTAs in patients with cancers. This review highlight clinical studies employing mRNA-LNPs encoding CTAs.

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Section: Mrna Vaccines As Anti-cancer Therapeuticsmentioning

confidence: 99%

Cancer/Testis Antigens as Targets for RNA-Based Anticancer Therapy

Shim,

Jo,

Jeoung

2023

IJMS

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“…It is possible that the spatial arrangement of translation complexes relative to other cell structures can serve as a factor that sets the desired orientation of higher-order protein complexes. Recently, such a mechanism was reconstituted in a cell lysate [ 228 ]: the authors were able to organize the structure of actin filaments in a certain way by localizing the transcripts encoding actin-binding protein using magnetic nanoparticles.…”

Section: Intracellular Transport Of Mrnas and Their Interaction With Cytoskeletal Elementsmentioning

confidence: 99%

mRNA Targeting, Transport and Local Translation in Eukaryotic Cells: From the Classical View to a Diversity of New Concepts

Lashkevich

Dmitriev

2021

Mol Biol

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Spatial organization of protein biosynthesis in the eukaryotic cell has been studied for more than fifty years, thus many facts have already been included in textbooks. According to the classical view, mRNA transcripts encoding secreted and transmembrane proteins are translated by ribosomes associated with endoplasmic reticulum membranes, while soluble cytoplasmic proteins are synthesized on free polysomes. However, in the last few years, new data has emerged, revealing selective translation of mRNA on mitochondria and plastids, in proximity to peroxisomes and endosomes, in various granules and at the cytoskeleton (actin network, vimentin intermediate filaments, microtubules and centrosomes). There are also long-standing debates about the possibility of protein synthesis in the nucleus. Localized translation can be determined by targeting signals in the synthesized protein, nucleotide sequences in the mRNA itself, or both. With RNA-binding proteins, many transcripts can be assembled into specific RNA condensates and form RNP particles, which may be transported by molecular motors to the sites of active translation, form granules and provoke liquid-liquid phase separation in the cytoplasm, both under normal conditions and during cell stress. The translation of some mRNAs occurs in specialized “translation factories,” assemblysomes, transperons and other structures necessary for the correct folding of proteins, interaction with functional partners and formation of oligomeric complexes. Intracellular localization of mRNA has a significant impact on the efficiency of its translation and presumably determines its response to cellular stress. Compartmentalization of mRNAs and the translation machinery also plays an important role in viral infections. Many viruses provoke the formation of specific intracellular structures, virus factories, for the production of their proteins. Here we review the current concepts of the molecular mechanisms of transport, selective localization and local translation of cellular and viral mRNAs, their effects on protein targeting and topogenesis, and on the regulation of protein biosynthesis in different compartments of the eukaryotic cell. Special attention is paid to new systems biology approaches, providing new cues to the study of localized translation.

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“…A recent study reported how microtubule-based active nematic gels, in contact with a thermotropic liquid crystal, can have their orientation dictated by a magnetic field (29). As magnetic interactions can be contactless, remote controlled and can deeply penetrate into thick materials, it could be advantageous to manipulate directly the constitutive elements of the active gel, as it has been shown for other biomolecules (30)(31)(32). In our study, we developed a strategy to label kinesin motors with magnetic nanoparticles in order to perturb the dynamical properties of a microtubule active gel.…”

Section: Introductionmentioning

confidence: 99%