mRNA vaccines in disease prevention and treatment

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

Published: Sept. 20, 2023

Abstract mRNA vaccines have emerged as highly effective strategies in the prophylaxis and treatment of diseases, thanks largely although not totally to their extraordinary performance recent years against worldwide plague COVID-19. The huge superiority regarding efficacy, safety, large-scale manufacture encourages pharmaceutical industries biotechnology companies expand application a diverse array despite nonnegligible problems design, fabrication, mode administration. This review delves into technical underpinnings vaccines, covering synthesis, delivery, adjuvant technologies. Moreover, this presents systematic retrospective analysis logical well-organized manner, shedding light on representative employed various diseases. scope extends across infectious cancers, immunological tissue damages, rare showcasing versatility potential therapeutic areas. Furthermore, engages prospective discussion current challenge direction for advancement utilization vaccines. Overall, comprehensive serves valuable resource researchers, clinicians, industry professionals, providing understanding aspects, historical context, future prospects fight

Language: Английский

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Path towards mRNA delivery for cancer immunotherapy from bench to bedside

Theranostics, Journal Year: 2023, Volume and Issue: 14(1), P. 96 - 115

Published: Oct. 30, 2023

Messenger RNA (mRNA) has emerged as a promising therapeutic agent for the prevention and treatment of various diseases. mRNA vaccines, in particular, offer an alternative approach to conventional boasting high potency, rapid development capabilities, cost-effectiveness, safe administration. However, clinical application vaccines is hindered by challenges instability inefficient

Language: Английский

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mRNA-based vaccines – global approach, challenges, and could be a promising wayout for future pandemics

Pharmaceutical Development and Technology, Journal Year: 2024, Volume and Issue: 29(6), P. 559 - 565

Published: May 30, 2024

mRNA-based vaccines are assured to significantly boost biopharmaceuticals since outbreak of coronavirus disease- 2019. Respiratory infections, such as influenza, SARS, MERS, COVID-19, and respiratory syncytial virus, often have high transmission rates due their airborne spread. infections can lead severe illness death. These outbreaks cause substantial economic social disruption, seen with the COVID-19 pandemic. In our interconnected world, diseases spread rapidly across borders. (e.g., mRNA-1283) reduce by creating immunity in population, thus lowering incidence these diseases. Vaccines crucial for global health security, helping prevent local from becoming pandemics. Nevertheless, various concerns remain intracellular delivery, susceptibility degradation catalytic hydrolysis, instability several physiological conditions. Therefore, an hour needed address challenges opportunities attaining high-quality stable novel drug delivery systems. The authors contributed extensive review clinical development, progress stability mitigate market needs. addition, discuss advances growth date; which dominate scope therapeutic implementation. Finally, recent trials, adjuvant benefits, prospects discussed.

Language: Английский

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An HTLV-1 envelope mRNA vaccine is immunogenic and protective in New Zealand rabbits

Journal of Virology, Journal Year: 2024, Volume and Issue: 98(2)

Published: Jan. 9, 2024

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus responsible for adult leukemia/lymphoma, severe and fatal CD4+ malignancy. Additionally, HTLV-1 can lead to chronic progressive neurodegenerative disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis. Unfortunately, the prognosis HTLV-1-related diseases generally poor, effective treatment options are limited. In this study, we designed synthesized codon optimized envelope (Env) mRNA encapsulated in lipid nanoparticle (LNP) evaluated its efficacy vaccine candidate an established rabbit model of infection persistence. Immunization regimens included prime/boost protocol using Env mRNA-LNP or control green fluorescent protein (GFP) mRNA-LNP. After immunization, rabbits were challenged by intravenous injection with irradiated producing cells. Three partially protected three completely against challenge. These then rechallenged 15 weeks later, two maintained sterilizing immunity. immunized rabbits, proviral load viral gene expression significantly lower. challenge vaccinated increase both CD4+/IFN-γ+ CD8+/IFN-γ+ T-cells was detected when stimulating overlapping peptides. elicited detectable anti-Env antibody response after vaccination all animals higher levels neutralizing activity. Neutralizing activity correlated reduction load. findings hold promise development preventive strategies therapeutic interventions associated diseases.IMPORTANCEmRNA technology has proven be viable approach effectively triggering immune responses that protect limit infections disease. our human delivered approach. The produced protective preclinical model. primarily transmitted through direct cell-to-cell contact, protection offered vaccines could have significant implications optimizing other candidates. This particularly important addressing enhancing rely on transmission.

Language: Английский

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A novel ADP-directed chaperone function facilitates the ATP-driven motor activity of SARS-CoV helicase

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(3)

Published: Jan. 24, 2025

Abstract Helicase is a nucleic acid motor that catalyses the unwinding of double-stranded (ds) RNA and DNA via ATP hydrolysis. Helicases can act either as unwinds its ds substrates or chaperone alters stability substrates, but two activities have not yet been reported to simultaneously. Here, we used single-molecule techniques unravel synergistic coordination helicase activities, found severe acute respiratory syndrome coronavirus (nsp13) capable modes action: (i) binding nsp13 in tandem with fork junction substrate mechanically by an ATP-driven synchronous power stroke; (ii) free nsp13, which bound complexed ADP solution, destabilizes through collisions between transient unbinding events unprecedented melting capability. Our findings provide new insights into how same enzyme works on different parts synergistically reaction, utilizing recycling by-product energy source.

Language: Английский

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Harnessing RNA therapeutics: novel approaches and emerging strategies for cardiovascular disease management

Frontiers in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 12

Published: March 20, 2025

RNA therapeutics are emerging as a promising approach for cardiovascular diseases (CVDs) management, offering targeted gene regulation through modalities like mRNA, siRNA, and miRNA. In recent years, researchers have conducted lot of research on the application technology in treatment CVDs. Despite hurdles off-target effects immune responses, clinical trial outcomes encouraging. This review synthesizes current progress CVDs, examining their mechanisms, advantages, challenges delivery safety. We highlight potential personalized medicine, combination artificial intelligence (AI) bioinformatics advancing therapeutics. The future CVDs is poised significant impact, necessitating continued interdisciplinary collaboration to optimize these treatments ensure patient safety efficacy.

Language: Английский

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Progress and Challenges in HIV-1 Vaccine Research: A Comprehensive Overview

Vaccines, Journal Year: 2025, Volume and Issue: 13(2), P. 148 - 148

Published: Jan. 31, 2025

The development of an effective HIV-1 vaccine remains a formidable challenge in biomedical research. Despite significant advancements our understanding HIV biology and pathogenesis, progress has been impeded by factors such as the virus's genetic diversity, high mutation rates, its ability to establish latent reservoirs. Recent innovative approaches, including mosaic vaccines mRNA technology induce broadly neutralizing antibodies, have shown promise. However, efficacy these modest, with best results achieving approximately 30% effectiveness. Ongoing research emphasizes necessity multifaceted strategy overcome obstacles achieve breakthrough development. This review summarizes current approaches utilized further understand create global vaccine. We discuss impact on for other diseases, COVID-19, influenza, Zika virus. Additionally, we highlight specific limitations faced each approach present methods researchers employ challenges. These techniques, which demonstrated preclinical clinical success, advanced field closer ultimate goal developing Leveraging will enable strides combating infectious ultimately improving health outcomes.

Language: Английский

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COVID‐19 post‐vaccination lymphadenopathy: A review of the use of fine needle aspiration cytology

Cytopathology, Journal Year: 2023, Volume and Issue: 34(5), P. 423 - 432

Published: Feb. 18, 2023

Abstract COVID‐19 vaccine‐associated clinical lymphadenopathy (C19‐LAP) and subclinical (SLDI), which are mainly detected by 18F‐FDG PET‐CT, have been observed after the introduction of RNA‐based vaccines during pandemic. Lymph node (LN) fine needle aspiration cytology (FNAC) has used to diagnose single cases or small series SLDI C19‐LAP. In this review, LN‐FNAC features C19‐LAP reported compared non‐Covid (NC)‐LAP. A search for studies on histopathology cytopathology was performed PubMed Google Scholar, 11 January 2023. Reports were retrieved. total 14 reports, plus one unpublished case in our institution, diagnosed included a pooled analysis corresponding histopathological reports. total, 26 with mean age 50.5 years. Twenty‐one lymphadenopathies assessed as benign, three atypical lymphoid hyperplasia; latter subsequently confirmed benign (one repetition LN‐FNAC, two histological control). One mediastinal patient suffering from melanoma reactive granulomatous inflammation, while unsuspected metastasis melanoma. all cases, cytological diagnoses follow‐up excisional biopsy. The high diagnostic value excluding malignant processes extremely useful context may be particularly valuable when CNB excisions difficult perform, Covid lockdowns.

Language: Английский

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ACE mRNA (Additional Chimeric Element incorporated IVT mRNA) for Enhancing Protein Expression by Modulating Immunogenicity

Advanced Science, Journal Year: 2024, Volume and Issue: 11(18)

Published: March 6, 2024

Abstract The development of in vitro transcribed mRNA (IVT mRNA)‐based therapeutics/vaccines depends on the management IVT immunogenicity. mRNA, which is used for intracellular protein translation, often triggers unwanted immune responses, interfering with expression and leading to reduced therapeutic efficacy. Currently, predominant approach mitigating responses involves incorporation costly chemically modified nucleotides like pseudouridine (Ψ) or N1‐methylpseudouridine (m1Ψ) into raising concerns about expense potential misincorporation amino acids codon sequences. Here, an Additional Chimeric Element incorporated (ACE mRNA), a novel incorporating two segments within single structure, introduced. first segment retains conventional components prepared unmodified nucleotides, while second, comprised RNA/DNA chimeric elements, aims modulate Notably, ACE demonstrates noteworthy reduction immunogenicity concurrently demonstrating enhanced efficiency. are based ability elements restrict retinoic acid‐inducible gene I (RIG‐I) stimulator interferon genes (STING)‐mediated activation. developed shows great modulating without need thereby advancing safety efficacy mRNA‐based therapeutics/vaccines.

Language: Английский

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Updated Considerations for the Immunopharmacological Aspects of the “Talented mRNA Vaccines”

Vaccines, Journal Year: 2023, Volume and Issue: 11(9), P. 1481 - 1481

Published: Sept. 12, 2023

Messenger RNA (mRNA) vaccines belong to a new class of medications, therapeutics, including both coding and non-coding RNAs. The use mRNA as therapy is based on the biological role itself, namely its translation into functional protein. goal produce specific antigen in cells elicit an immune response that might be prophylactic or therapeutic. potential vaccine has been envisaged for years but efficacy clearly demonstrated with approval COVID-19 2021. Since then, have pipeline diseases are still untreatable. There many advantages over traditional vaccines, easy cost-effective production, high safety, high-level expression. However, nature itself some technical issues pose challenges associated vaccines' development use. Here we review immunological pharmacological features by discussing their pharmacokinetics, mechanisms action, particular attention related administration. Furthermore, present overview areas application clinical trials utilize treatment.

Language: Английский

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