Synthesis and assembly of human vault particles in yeast

Wang, Meng; Kickhoefer, Valerie A.; Rome, Leonard H.; Foellmer, Oliver K.; Mahendra, Shaily

doi:10.1002/bit.26825

Cited by 16 publications

(21 citation statements)

References 45 publications

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“…Yeast have been successfully used in the last decades for recombinant protein production [64] and, for the synthesis of protein nanostructures such as virus-like particles [65], are similar in size and structure to vaults. In this context, it has been recently described for the first time the production of vaults in the yeast Pichia pastoris [66]. Expression of MVP alone in P. pastoris led to the formation of intact vaults, morphologically similar to endogenous vaults isolated from other eukaryotes.…”

Section: Recombinant Vaults Production and Purificationmentioning

confidence: 99%

Latest Advances in the Development of Eukaryotic Vaults as Targeted Drug Delivery Systems

et al. 2019

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The use of smart drug delivery systems (DDSs) is one of the most promising approaches to overcome some of the drawbacks of drug-based therapies, such as improper biodistribution and lack of specific targeting. Some of the most attractive candidates as DDSs are naturally occurring, self-assembling protein nanoparticles, such as viruses, virus-like particles, ferritin cages, bacterial microcompartments, or eukaryotic vaults. Vaults are large ribonucleoprotein nanoparticles present in almost all eukaryotic cells. Expression in different cell factories of recombinant versions of the “major vault protein” (MVP) results in the production of recombinant vaults indistinguishable from native counterparts. Such recombinant vaults can encapsulate virtually any cargo protein, and they can be specifically targeted by engineering the C-terminus of MVP monomer. These properties, together with nanometric size, a lumen large enough to accommodate cargo molecules, biodegradability, biocompatibility and no immunogenicity, has raised the interest in vaults as smart DDSs. In this work we provide an overview of eukaryotic vaults as a new, self-assembling protein-based DDS, focusing in the latest advances in the production and purification of this platform, its application in nanomedicine, and the current preclinical and clinical assays going on based on this nanovehicle.

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Section: Recombinant Vaults Production and Purificationmentioning

confidence: 99%

Latest Advances in the Development of Eukaryotic Vaults as Targeted Drug Delivery Systems

et al. 2019

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“…The minimum vault structure, endowed with its natural morphology, can be produced by expression of the sole MVP in insect cells [14,15]. More recently, recombinant vault nanoparticles were produced in the methylotropic yeast Pichia pastoris and were proven to be morphologically indistinguishable from those produced in insect cells [16]. A singular trait of the vault nanoparticle is the way it assembles, as it was shown that biosynthesis and assembling of MVP subunits take place sequentially at the level of polyribosomes, which therefore act similar to a 3D nanoprinter [15].…”

Section: Introductionmentioning

confidence: 99%

The Vault Nanoparticle: A Gigantic Ribonucleoprotein Assembly Involved in Diverse Physiological and Pathological Phenomena and an Ideal Nanovector for Drug Delivery and Therapy

Frascotti

Galbiati

Mazzucchelli

et al. 2021

Cancers

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The vault nanoparticle is a eukaryotic ribonucleoprotein complex consisting of 78 individual 97 kDa-“major vault protein” (MVP) molecules that form two symmetrical, cup-shaped, hollow halves. It has a huge size (72.5 × 41 × 41 nm) and an internal cavity, wherein the vault poly(ADP-ribose) polymerase (vPARP), telomerase-associated protein-1 (TEP1), and some small untranslated RNAs are accommodated. Plenty of literature reports on the biological role(s) of this nanocomplex, as well as its involvement in diseases, mostly oncological ones. Nevertheless, much has still to be understood as to how vault participates in normal and pathological mechanisms. In this comprehensive review, current understanding of its biological roles is discussed. By different mechanisms, vault’s individual components are involved in major cellular phenomena, which result in protection against cellular stresses, such as DNA-damaging agents, irradiation, hypoxia, hyperosmotic, and oxidative conditions. These diverse cellular functions are accomplished by different mechanisms, mainly gene expression reprogramming, activation of proliferative/prosurvival signaling pathways, export from the nucleus of DNA-damaging drugs, and import of specific proteins. The cellular functions of this nanocomplex may also result in the onset of pathological conditions, mainly (but not exclusively) tumor proliferation and multidrug resistance. The current understanding of its biological roles in physiological and pathological processes should also provide new hints to extend the scope of its exploitation as a nanocarrier for drug delivery.

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“…(H, I) Illustration and AFM image of a DNA origami box encapsulated with proteins. Reproduced with permission from (A) ref , copyright 1992 American Chemical Society; (B) ref , copyright 2006 Wiley; (D) ref , copyright 2014 American Chemical Society; (E) ref , copyright 2012 Nature Publishing Group; (F) ref , copyright 2018 Wiley; (G) ref , copyright 2014 Royal Society of Chemistry; (I) ref , copyright 2012 American Chemical Society.…”

Section: Introductionmentioning

confidence: 99%

Nanomaterial-Supported Enzymes for Water Purification and Monitoring in Point-of-Use Water Supply Systems

2019

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Conspectus Increasing pollution of global water sources and challenges in rapid detection and treatment of the wide range of contaminants pose considerable burdens on public health. The issue is particularly critical in rural areas, where building of centralized water treatment systems and pipe infrastructure to connect dispersed populations is not always practical. Point-of-use (POU) water supply systems provide cost-effective and energy-efficient approaches to store, treat, and monitor the quality of water. Currently available POU systems have limited success in dealing with the portfolio of emerging contaminants, particularly those present at trace concentrations. A site-to-site variation in contaminant species and concentrations also requires versatile POU systems to detect and treat contaminants and provide on-demand clean water. Among different technologies for developing rapid and sensitive water purification processes and sensors, enzymes offer one of the potential solutions because of their strong activity and selectivity toward chemical substrates. Many enzyme–nanomaterial composites have recently been developed that enhance enzymes’ stability and activity and expand their functionality, thus facilitating the application of nanosupported enzymes in advanced POU systems. In this Account, we highlight the strengths and limitations of nanosupported enzymes for their potential applications in POU systems for water treatment as well as detection of contaminants, even at trace levels. We first summarize the mechanisms by which silica, carbon, and metallic nanosupports improve enzyme stability, selectivity, and catalysis. The unique immobilization properties and potential advantages of novel bioderived nanosupports over non-bioderived nanomaterials are emphasized. We illustrate prospective applications of nanosupported enzymes in POU systems with different roles: water purification, disinfection, and contaminant sensing. For each type of application, nanosupported enzymes offer higher performance than free enzymes. Nanosupports prolong enzymes’ lifetimes and improve the rates of contaminant removal by concentrating contaminants near the enzymes. Nanosupports also stabilize antimicrobial enzymes while facilitating their attachment to bacterial surfaces, thereby increasing their potential uses for disinfection and prevention of biofouling in water purification and storage devices. As enzyme-based electrochemical sensors rely on electrochemical reactions of enzymatically generated species, the ability of conductive nanosupports to enhance enzyme activity and stability and to promote transfer of electrons onto the electrode greatly improves the sensitivity and durability of electroenzymatic contaminant sensors. Despite the promising results in laboratory settings, the application of nanosupported enzymes in real-world POU systems requires the implementation of multiple enzyme combinations and strategies for minimizing health risks associated with unintended releases of nanomaterials. Finally, we identify multidisc...

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Synthesis and assembly of human vault particles in yeast

Cited by 16 publications

References 45 publications

Latest Advances in the Development of Eukaryotic Vaults as Targeted Drug Delivery Systems

Latest Advances in the Development of Eukaryotic Vaults as Targeted Drug Delivery Systems

The Vault Nanoparticle: A Gigantic Ribonucleoprotein Assembly Involved in Diverse Physiological and Pathological Phenomena and an Ideal Nanovector for Drug Delivery and Therapy

Nanomaterial-Supported Enzymes for Water Purification and Monitoring in Point-of-Use Water Supply Systems

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