The landscape of mRNA nanomedicine

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(11), P. 2273 - 2287

Published: Nov. 1, 2022

Language: Английский

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Lipid nanoparticle-mediated lymph node–targeting delivery of mRNA cancer vaccine elicits robust CD8 ⁺ T cell response

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(34)

Published: Aug. 15, 2022

The targeted delivery of messenger RNA (mRNA) to desired organs remains a great challenge for in vivo applications mRNA technology. For vaccines, the lymph node (LN) is predicted reduce side effects and increase immune response. In this study, we explored an endogenously LN-targeting lipid nanoparticle (LNP) without modification any active targeting ligands developing cancer vaccine. LNP named 113-O12B showed increased specific expression LN compared with formulated ALC-0315, synthetic used COVID-19 vaccine Comirnaty. CD8 + T cell response encoded full-length ovalbumin (OVA) model antigen. As result, protective therapeutic effect OVA-encoding on OVA-antigen–bearing B16F10 melanoma was also improved. Moreover, encapsulated TRP-2 peptide (TRP2 180–188 )–encoding exhibited excellent tumor inhibition, complete 40% regular when combined anti–programmed death-1 (PD-1) therapy, revealing broad application from protein antigens. All treated mice long-term memory, hindering occurrence metastatic nodules lung rechallenging experiments that followed. enhanced antitumor efficacy system shows potential as universal platform next generation vaccines.

Language: Английский

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Circular RNA vaccine in disease prevention and treatment

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Sept. 11, 2023

Abstract CircRNAs are a class of single-stranded RNAs with covalently linked head-to-tail topology. In the decades since its initial discovery, their biogenesis, regulation, and function have rapidly disclosed, permitting better understanding adoption them as new tools for medical applications. With development biotechnology molecular medicine, artificial circRNAs been engineered novel vaccines disease treatment prevention. Unlike linear mRNA vaccine which applications were limited by instability, inefficiency, innate immunogenicity, circRNA incorporate internal ribosome entry sites (IRESs) open reading frame (ORF) provides an improved approach to RNA-based vaccination safety, stability, simplicity manufacture, scalability. However, at early stage, optimization, delivery require further evaluation. this review, we comprehensively describe vaccine, including history superiority. We also summarize discuss current methodological research preparation, design, synthesis, purification. Finally, highlight options potential in diseases Considering unique high low protein/peptide-coding capacity special closed-loop construction, circRNA-based therapeutic platforms may superior application prospects broad range diseases.

Language: Английский

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Physiological Barriers and Strategies of Lipid‐Based Nanoparticles for Nucleic Acid Drug Delivery

Advanced Materials, Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 4, 2023

Abstract Lipid‐based nanoparticles (LBNPs) are currently the most promising vehicles for nucleic acid drug (NAD) delivery. Although their clinical applications have achieved success, NAD delivery efficiency and safety still unsatisfactory, which are, to a large extent, due existence of multi‐level physiological barriers in vivo. It is important elucidate interactions between these LBNPs, will guide more rational design efficient with low adverse effects facilitate broader therapeutics. This review describes obstacles challenges biological at systemic, organ, sub‐organ, cellular, subcellular levels. The strategies overcome comprehensively reviewed, mainly including physically/chemically engineering LBNPs directly modifying by auxiliary treatments. Then potentials successful translation preclinical studies into clinic discussed. In end, forward look on manipulating protein corona (PC) addressed, may pull off trick overcoming those significantly improve efficacy LBNP‐based NADs

Language: Английский

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Two Green Micellar HPLC and Mathematically Assisted UV Spectroscopic Methods for the Simultaneous Determination of Molnupiravir and Favipiravir as a Novel Combined COVID-19 Antiviral Regimen

Molecules, Journal Year: 2022, Volume and Issue: 27(7), P. 2330 - 2330

Published: April 4, 2022

Following the spread of COVID-19 pandemic crisis, a race was initiated to find successful regimen for postinfections. Among those trials, recent study declared efficacy an antiviral combination favipiravir (FAV) and molnupiravir (MLP). The combined helped in 60% eradication SARS-CoV-2 virus from lungs studied hamster models. Moreover, it prevented viral transmission cohosted sentinels. Because both medications are orally bioavailable, coformulation FAV MLP can be predicted. developed is aimed at developing new green simple methods simultaneous determination then their application dissolution behavior if coformulated together. A micellar HPLC method validated using RP-C18 core-shell column (5 μm, 150 × 4.6 mm) isocratic mixed mobile phase composed 0.1 M SDS, 0.01 Brij-35, 0.02 monobasic potassium phosphate mixture adjusted pH 3.1 1.0 mL min-1 flow rate. analytes were detected 230 nm. run time less than five minutes under optimized chromatographic conditions. Four other multivariate chemometric model validated, namely, classical least square (CLS), principal component regression (PCR), partial squares (PLS-1), genetic algorithm-partial (GA-PLS-1). models succeeded resolving great similarity overlapping UV spectra unlike traditional univariate methods. All organic solvent-free, did not require extraction or derivatization steps, applied construction profile tablets capsules. revealed that amount simultaneously released cited drugs increases up until reaching plateau after 15 20 min MLP, respectively. greenness assessed on GAPI found harmony with analytical chemistry concepts.

Language: Английский

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Understanding the Pharmacology of COVID-19 mRNA Vaccines: Playing Dice with the Spike?

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(18), P. 10881 - 10881

Published: Sept. 17, 2022

Coronavirus disease-19 (COVID-19) mRNA vaccines are the mainstays of mass vaccination campaigns in most Western countries. However, emergency conditions which their development took place made it impossible to fully characterize effects and mechanism action. Here, we summarize discuss available evidence indicating that COVID-19 better reflect pharmaceutical drugs than conventional vaccines, as they do not contain antigens but an active SARS-CoV-2 S protein mRNA, representing at same time principle a prodrug, upon intracellular translation results endogenous production protein. Both vaccine-derived resulting exhibit complex pharmacology undergo systemic disposition. Defining has straightforward implications for pharmacodynamic, pharmacokinetic, clinical post-marketing safety assessment. Only accurate characterization will guarantee safe, rational individualized use these products.

Language: Английский

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Current Evidence in SARS-CoV-2 mRNA Vaccines and Post-Vaccination Adverse Reports: Knowns and Unknowns

Diagnostics, Journal Year: 2022, Volume and Issue: 12(7), P. 1555 - 1555

Published: June 26, 2022

The novel mRNA vaccinations against COVID-19 are gaining worldwide attention for their potential efficacy, as well the diagnosis of some post-vaccination-reported adverse reactions. In this state-of-the-art review article, we present current evidence regarding mainly spontaneous allergic reactions, skin occurrences, vascular, blood, endocrine and heart events, respiratory reports, gastrointestinal, hepatic kidney reproductive pregnancy issues muscle ear, eye, neurologic psychiatric events following vaccination COVID-19. We further strategies, provide important information side effects associated with spike protein based LNP-mRNA vaccine its adjuvants, all possible dangerous roles protein, discuss our expert opinion on knowns unknowns towards topic.

Language: Английский

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The Metaverse as a Virtual Model of Platform Urbanism: Its Converging AIoT, XReality, Neurotech, and Nanobiotech and Their Applications, Challenges, and Risks

Smart Cities, Journal Year: 2023, Volume and Issue: 6(3), P. 1345 - 1384

Published: May 11, 2023

With their exponentially rising computational power, digital platforms are heralding a new era of hybrid intelligence. There has recently been much enthusiasm and hype that the Metaverse potential to unlock This is premised on idea represents an applied convergence Artificial Intelligence Things (AIoT) Extended Reality (XR) intersects with urbanism in terms distinctive features platform-mediated everyday life experiences cities. However, social interaction its resulting organization mediated governed by algorithms thus submitted to—a dream of—complete logical ordering. raises plethora concerns related systemic collection algorithmic processing users’ personal, brain, biometric data, i.e., profound societal—and hardest predict ethical—implications. Therefore, this study analyzes synthesizes large body scientific literature unfolding AIoT XR technologies, neurotechnology, nanobiotechnology realm order derive novel conceptual framework for as envisioned virtual model platform urbanism. Further, it examines key challenges risks these converging technologies relation beyond. employs thematic analysis synthesis cope multidisciplinary literature. The identifies seven themes: (1) Platformization, (2) urbanism, (3) (4) (5) (6) (7) nanobiotechnology. synthesized evidence reveals that, while neurotechnology have numerous benefits promising prospects, they raise contentions controversies stemming from use inflict harm human users—if left unchecked—through black box mediation underpinning Metaverse. findings serve steer contribute flourishing wellbeing adhering upholding ethical principles well leveraging underlying disruptive meaningful ways. They also aid scholars, practitioners, policymakers assessing pros cons especially inevitable ramifications.

Language: Английский

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Immune Response and Molecular Mechanisms of Cardiovascular Adverse Effects of Spike Proteins from SARS-CoV-2 and mRNA Vaccines

Biomedicines, Journal Year: 2023, Volume and Issue: 11(2), P. 451 - 451

Published: Feb. 3, 2023

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus responsible for the COVID-19 disease) uses Spike proteins of its envelope infecting target cells expressing on membrane angiotensin converting enzyme 2 (ACE2) that acts as a receptor. To control pandemic, genetically engineered vaccines have been designed inducing neutralizing antibodies against proteins. These do not act like traditional protein-based vaccines, they deliver message in form mRNA or DNA to host then produce and expose protein (from which it can be shed soluble form) alert immune system. Mass vaccination has brought light various adverse effects associated with these based mainly affecting circulatory cardiovascular ACE2 is present membrane-bound several cell types, including mucosa upper gastrointestinal tracts, endothelium, platelets, plasma. converts vasoconstrictor II into peptides vasodilator properties. Here we review pathways immunization molecular mechanisms through protein, either from encoded by mRNA-based interferes Renin-Angiotensin-System governed ACE2, thus altering homeostasis circulation Understanding interactions consequent impact system will direct diagnosis therapy vaccine-related provide information development personalized considers pathophysiological conditions predisposing such events.

Language: Английский

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Circular RNA vaccines with long-term lymph node-targeting delivery stability after lyophilization induce potent and persistent immune responses

mBio, Journal Year: 2023, Volume and Issue: 15(1)

Published: Dec. 11, 2023

messenger RNA (mRNA) vaccines are a key technology in combating existing and emerging infectious diseases. However, the inherent instability of mRNA nonspecificity lipid nanoparticle-encapsulated (LNP) delivery systems result need for cold storage relatively short-duration immune response to vaccines. Herein, we develop novel vaccine form circRNAs encapsulated LNPs, circular structure enhances their stability. Lyophilization is considered most effective method long-term preservation this process may irreversible damage nanoparticles, particularly potential disruption targeting modifications on LNPs. During selection lymph node-targeting ligands, found that LNPs modified with mannose maintained physical properties almost unchanged after lyophilization. Additionally, specificity immunogenicity remained unaffected. In contrast, even addition cryoprotectants such as sucrose, were impaired, leading an obvious decrease immunogenicity. This be attributed protective role surface during Freshly prepared lyophilized mLNP-circRNA elicited comparable responses both rabies virus model SARS-CoV-2 model. Our data demonstrated elicit robust while improving stability lyophilization, no compromise tissue specificity. Therefore, mannose-modified LNP-circRNA represent promising design strategy.

Language: Английский

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