Viral Membrane Fusion Proteins and RNA Sorting Mechanisms for the Molecular Delivery by Exosomes

Zubarev, I. V.; Vladimirtsev, Dmitry; Воронцова, М. А.; Blatov, Igor; Шевченко, К. Г.; Zvereva, Svetlana; Lunev, Evgenii A.; Файзулоев, Е. Б.; Barlev, Nikolay

doi:10.20944/preprints202110.0130.v1

Cited by 5 publications

(1 citation statement)

References 151 publications

(158 reference statements)

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“…The most common vectors for gene transport are viruses and plasmids, which are highly virulent and rarely specific [22]. sEVs with 50-150 nm diameter that have been shown to contain proteins, DNA, RNA, lipids and various metabolites that have potential inflammatory and immunomodulatory functions [23,24].…”

Section: Introductionmentioning

confidence: 99%

Small extracellular vesicles derived from Nrf2-overexpressing human amniotic mesenchymal stem cells protect against lipopolysaccharide-induced acute lung injury by inhibiting NLRP3

Zhu

et al. 2022

Biol Direct

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Background Acute lung injury (ALI) is a major cause of respiratory failure in critically ill patients that results in significant morbidity and mortality. Recent studies indicate that cell-based therapies may be beneficial in the treatment of ALI. We recently demonstrated that Nrf2-overexpressing human amniotic mesenchymal stem cells (hAMSCs) reduce lung injury, fibrosis and inflammation in lipopolysaccharide (LPS)-challenged mice. Here we tested whether small extracellular vesicles (sEVs) derived from Nrf2-overexpressing hAMSCs (Nrf2-sEVs) could protect against ALI. sEVs were isolated from hAMSCs that overexpressed (Nrf2-sEVs) or silenced (siNrf2-sEVs) Nrf2. We examined the effects of sEVs treatment on lung inflammation in a mouse model of ALI, where LPS was administered intratracheally to mice, and lung tissues and bronchoalveolar lavage fluid (BALF) were analyzed 24 h later. Methods Histological analysis, immunofluorescence microscopy, western blotting, RT-PCR and ELISA were used to measure the inflammatory response in the lungs and BALF. Results We found that sEVs from hAMSCs are protective in ALI and that Nrf2 overexpression promotes protection against lung disease. Nrf2-sEVs significantly reduced lung injury in LPS-challenged mice, which was associated with decreased apoptosis, reduced infiltration of neutrophils and macrophages, and inhibition of pro-inflammatory cytokine expression. We further show that Nrf2-sEVs act by inhibiting the activation of the NLRP3 inflammasome and promoting the polarization of M2 macrophages. Conclusion Our data show that overexpression of Nrf2 protects against LPS-induced lung injury, and indicate that a novel therapeutic strategy using Nrf2-sEVs may be beneficial against ALI.

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Section: Introductionmentioning

confidence: 99%

Small extracellular vesicles derived from Nrf2-overexpressing human amniotic mesenchymal stem cells protect against lipopolysaccharide-induced acute lung injury by inhibiting NLRP3

Zhu

et al. 2022

Biol Direct

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New Therapeutics for Extracellular Vesicles: Delivering CRISPR for Cancer Treatment

Yan

Liang

2022

IJMS

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Cancers are defined by genetic defects, which underlines the prospect of using gene therapy in patient care. During the past decade, CRISPR technology has rapidly evolved into a powerful gene editing tool with high fidelity and precision. However, one of the impediments slowing down the clinical translation of CRISPR-based gene therapy concerns the lack of ideal delivery vectors. Extracellular vesicles (EVs) are nano-sized membrane sacs naturally released from nearly all types of cells. Although EVs are secreted for bio-information conveyance among cells or tissues, they have been recognized as superior vectors for drug or gene delivery. Recently, emerging evidence has spotlighted EVs in CRISPR delivery towards cancer treatment. In this review, we briefly introduce the biology and function of the CRISPR system and follow this with a summary of current delivery methods for CRISPR applications. We emphasize the recent progress in EV-mediated CRISPR editing for various cancer types and target genes. The reported strategies for constructing EV-CRISPR vectors, as well as their limitations, are discussed in detail. The review aims to throw light on the clinical potential of engineered EVs and encourage the expansion of our available toolkit to defeat cancer.

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Genetically Encoded Self-Assembling Protein Nanoparticles for the Targeted Delivery In Vitro and In Vivo

et al. 2023

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Targeted nanoparticles of different origins are considered as new-generation diagnostic and therapeutic tools. However, there are no targeted drug formulations within the composition of nanoparticles approved by the FDA for use in the clinic, which is associated with the insufficient effectiveness of the developed candidates, the difficulties of their biotechnological production, and inadequate batch-to-batch reproducibility. Targeted protein self-assembling nanoparticles circumvent this problem since proteins are encoded in DNA and the final protein product is produced in only one possible way. We believe that the combination of the endless biomedical potential of protein carriers as nanoparticles and the standardized protein purification protocols will make significant progress in “magic bullet” creation possible, bringing modern biomedicine to a new level. In this review, we are focused on the currently existing platforms for targeted self-assembling protein nanoparticles based on transferrin, lactoferrin, casein, lumazine synthase, albumin, ferritin, and encapsulin proteins, as well as on proteins from magnetosomes and virus-like particles. The applications of these self-assembling proteins for targeted delivery in vitro and in vivo are thoroughly discussed, including bioimaging applications and different therapeutic approaches, such as chemotherapy, gene delivery, and photodynamic and photothermal therapy. A critical assessment of these protein platforms’ efficacy in biomedicine is provided and possible problems associated with their further development are described.

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Viral Membrane Fusion Proteins and RNA Sorting Mechanisms for the Molecular Delivery by Exosomes

Cited by 5 publications

References 151 publications

Small extracellular vesicles derived from Nrf2-overexpressing human amniotic mesenchymal stem cells protect against lipopolysaccharide-induced acute lung injury by inhibiting NLRP3

Small extracellular vesicles derived from Nrf2-overexpressing human amniotic mesenchymal stem cells protect against lipopolysaccharide-induced acute lung injury by inhibiting NLRP3

New Therapeutics for Extracellular Vesicles: Delivering CRISPR for Cancer Treatment

Genetically Encoded Self-Assembling Protein Nanoparticles for the Targeted Delivery In Vitro and In Vivo

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