Innovations in RNA therapeutics: a review of recent advances and emerging technologies

Nucleosides Nucleotides & Nucleic Acids, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 25

Published: Jan. 13, 2025

The field of biomedical science has witnessed another milestone with the advent RNA-based therapeutics. This review explores three major RNA molecules, namely: messenger (mRNA), interference technology (RNAi), and Antisense Oligonucleotide (ASO), analyses U.S. Food Drug Administration drugs from 14 pharmaceutical companies in terms targeted genes, diseases types, clinical trials status, mode delivery, year production. Many such are clinically approved or pending approval by (FDA) alongside other leading agencies. Regarding diseases, this article emphasizes cancer therapy, genetic viral infections, two categories drug delivery systems include vectors nanoparticles. Despite tremendous progress made, key issues associated these stability, off-target activities payloads, efficiency cellular uptake, innovative need for engineering techniques modifications. transformative potential therapeutics role technologies addressing needs, paving way a new era precision medicine.

Language: Английский

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The Role of Memory T-Cell Mediated Immunity in Long-term COVID-19: Effects of Vaccination Status.

PubMed, Journal Year: 2025, Volume and Issue: 50(2), P. 61 - 68

Published: Feb. 1, 2025

T-cell-mediated immunity is essential for controlling severe acute respiratory syndrome coronavirus 2 (SARSCoV2) infection, preventing disease, and potentially reducing the risk of long-term disease (COVID). This study investigated impact natural vaccination, hybrid on T-cell responses, with a particular emphasis role memory T-cells in COVID-19. The present reviewed current literature including development, individuals SARS-CoV-2 those vaccinated messenger RNA (mRNA) vaccines, immunity. It examined studies that compared activity, immune regulation, prevalence COVID-19 across these groups. Natural infection induces variable cases showing stronger but sometimes dysregulated immunological which may contribute to prolonged Vaccination, particularly mRNA elicits targeted consistent T-cells, severity, incidence Hybrid combines provides most robust protection, enhanceds reduces through balanced regulation. Memory play critical mitigating Vaccination significantly enhances immunity, minimizing chronic symptoms alone. effective defense, emphasizing importance even after prevent

Language: Английский

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COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 24, 2024

Our understanding of COVID-19 vaccinations and their impact on health mortality has evolved substantially since the first vaccine rollouts. Published reports from original randomized phase 3 trials concluded that mRNA vaccines could greatly reduce symptoms. In interim, problems with methods, execution, reporting these pivotal have emerged. Re-analysis Pfizer trial data identified statistically significant increases in serious adverse events (SAEs) group. Numerous SAEs were following Emergency Use Authorization (EUA), including death, cancer, cardiac events, various autoimmune, hematological, reproductive, neurological disorders. Furthermore, products never underwent adequate safety toxicological testing accordance previously established scientific standards. Among other major topics addressed this narrative review are published analyses harms to humans, quality control issues process-related impurities, mechanisms underlying (AEs), immunologic basis for inefficacy, concerning trends based registrational data. The risk-benefit imbalance substantiated by evidence date contraindicates further booster injections suggests that, at a minimum, should be removed childhood immunization program until proper studies conducted. Federal agency approval blanket-coverage population-wide had no support an honest assessment all relevant commensurate consideration risks versus benefits. Given extensive, well-documented unacceptably high harm-to-reward ratio, we urge governments endorse global moratorium modified questions pertaining causality, residual DNA, aberrant protein production answered.

Language: Английский

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Mutational dynamics of SARS-CoV-2: Impact on future COVID-19 vaccine strategies

Heliyon, Journal Year: 2024, Volume and Issue: 10(9), P. e30208 - e30208

Published: April 25, 2024

The rapid emergence of multiple strains Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has sparked profound concerns regarding the ongoing evolution virus and its potential impact on global health. Classified by World Health Organization (WHO) as variants concern (VOC), these exhibit heightened transmissibility pathogenicity, posing significant challenges to existing vaccine strategies. Despite widespread vaccination efforts, continual SARS-CoV-2 presents a formidable obstacle achieving herd immunity. Of particular is coronavirus spike (S) protein, pivotal viral surface protein crucial for host cell entry infectivity. Mutations within S have been shown enhance confer resistance antibody-mediated neutralization, undermining efficacy traditional platforms. Moreover, undergoes molecular under selective immune pressure, leading diverse with distinct mutation profiles. This review underscores urgent need vigilance adaptation in development efforts combat evolving landscape mutations ensure long-term effectiveness immunization campaigns.

Language: Английский

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COVID-19 Vaccines: Where Did We Stand at the End of 2023?

Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 203 - 203

Published: Jan. 29, 2024

Vaccine development against SARS-CoV-2 has been highly successful in slowing down the COVID-19 pandemic. A wide spectrum of approaches including vaccines based on whole viruses, protein subunits and peptides, viral vectors, nucleic acids developed parallel. For all types vaccines, good safety efficacy have obtained both preclinical animal studies clinical trials humans. Moreover, emergency use authorization granted for major vaccines. Although high demonstrated, rare cases severe adverse events detected after global mass vaccinations. Emerging variants possessing enhanced infectivity affected vaccine protection requiring re-design re-engineering novel candidates. Furthermore, insight is given into preparedness emerging variants.

Language: Английский

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S6P mutation in Delta and Omicron variant spike protein significantly enhances the efficacy of mRNA COVID-19 vaccines

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 3, 2025

The unrelenting emergence of SARS-CoV-2 variants has significantly challenged the efficacy existing COVID-19 vaccines. Enhancing stability and immunogenicity spike protein is critical for improving vaccine performance addressing variant-driven immune evasion. We developed an mRNA-based vaccine, RV-1730, encoding Delta variant with S6P mutation to enhance immunogenicity. vaccine's protective were evaluated in preclinical models, including monovalent (RV-1730) bivalent (RV-1731) formulations targeting BA.1 variants. Additionally, effectiveness RV-1730 as a heterologous booster following primary vaccination BNT162b2 (Pfizer-BioNTech) mRNA-1273 (Moderna-NIAID) was assessed. elicited stronger B T cell responses more durable neutralizing antibodies compared S2P-based RV-1731 demonstrated broad activity against emerging variants, XBB1.5 JN.1. Importantly, when used initial immunization or mRNA-1273, enhanced antibody titers multiple Omicron. Both provided superior protection indicating due mutation. incorporation into enhances strong broad-spectrum underscore their potential versatile effective strategies its evolving

Language: Английский

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Enhanced stability and efficacy of a lyophilized mRNA SARS-CoV-2 vaccine incorporating novel Ionizable lipids after one year storage at 25ºC

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

mRNA vaccines have shown great efficacy against SARS-CoV-2, yet challenges remain in optimizing vaccine components to achieve enhanced immune response and stability. In this study, we developed CPVax-CoV, a new lyophilized that features novel thiolactone-based ionizable lipids newly designed untranslated regions (UTRs) for expression. Incorporation of these optimized into our candidate CPVax-CoV significantly improved responses mice compared commercially available vaccines. Moreover, has proven be thermostable, maintaining its biological activity up one year at 4°C 25°C after lyophilization, overcoming the cold-chain limitations current This demonstrates protective ancestral SARS-CoV-2 Omicron XBB variant, offering scalable solution global distribution pandemic preparedness. These findings underscore potential platform future next-generation development.

Language: Английский

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Serosurveillance among urban slum and non-slum population immunized with COVID-19 vaccines in Bangladesh

Epidemiology and Infection, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 34

Published: Jan. 5, 2024

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Language: Английский

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Clinical development of SpikoGen®, an Advax-CpG55.2 adjuvanted recombinant spike protein vaccine

Human Vaccines & Immunotherapeutics, Journal Year: 2024, Volume and Issue: 20(1)

Published: June 5, 2024

Recombinant protein vaccines represent a well-established, reliable and safe approach for pandemic vaccination. SpikoGen® is recombinant spike trimer manufactured in insect cells formulated with Advax-CpG55.2 adjuvant. In murine, hamster, ferret non-human primate studies, consistently provided protection against range of SARS-CoV-2 variants. A pivotal Phase 3 placebo-controlled efficacy trial involving 16,876 participants confirmed the ability to prevent infection severe disease caused by virulent Delta strain. subsequently received marketing authorization from Iranian FDA early October 2021 prevention COVID-19 adults. Following successful pediatric study, its approval was extended children 5 years older. Eight million doses have been delivered, next-generation booster version currently development. This highlights benefits adjuvanted protein-based approaches which should not overlook when vaccine platforms are being selected future pandemics.

Language: Английский

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Opportunities and challenges to implementing mRNA-based vaccines and medicines: lessons from COVID-19

Frontiers in Public Health, Journal Year: 2024, Volume and Issue: 12

Published: Aug. 8, 2024

The messenger RNA (mRNA) platform emerged at the forefront of vaccine development during COVID-19 pandemic, with two mRNA vaccines being among first authorized globally. These were developed rapidly. Informed by decades laboratory research, and proved to be safe efficacious tools for mitigating global impact pandemic. holds promise a broader medical application beyond COVID-19. Herein, we provide an overview this describe lessons learned from pandemic help formulate strategies toward enhancing uptake future mRNA-based interventions. We identify several as vital acceptance expanding array therapeutics, including education, accurate transparent information sharing, targeted engagement campaigns, continued investment in safety surveillance, inclusion diverse participant pools clinical trials, addressing deep-rooted inequalities access healthcare. present findings Global Listening Project (GLP) initiative, which draws on quantitative qualitative approaches capture perceptions experiences design concrete action plans improving societal preparedness emergencies. GLP survey (>70,000 respondents 70 countries) revealed tremendous disparities across countries sociodemographic groups regarding willingness accept novel medicines. comfort innovations medicines was generally low (35%) marginally lower women (33%). learnt actionable insights into designing effective enhance

Language: Английский

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