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mRNA vaccines have been demonstrated as a powerful alternative to traditional conventional vaccines because of their high potency, safety and efficacy, capacity for rapid clinical development, and potential for rapid, low-cost manufacturing. These vaccines have progressed from being a mere curiosity to emerging as COVID-19 pandemic vaccine front-runners. The advancements in the field of nanotechnology for developing delivery vehicles for mRNA vaccines are highly significant. In this review we have summarized each and every aspect of the mRNA vaccine. The article describes the mRNA structure, its pharmacological function of immunity induction, lipid nanoparticles (LNPs), and the upstream, downstream, and formulation process of mRNA vaccine manufacturing. Additionally, mRNA vaccines in clinical trials are also described. A deep dive into the future perspectives of mRNA vaccines, such as its freeze-drying, delivery systems, and LNPs targeting antigen-presenting cells and dendritic cells, are also summarized.

mRNA vaccines have become a promising platform for cancer immunotherapy. During vaccination, naked or vehicle loaded mRNA vaccines efficiently express tumor antigens in antigen-presenting cells (APCs), facilitate APC activation and innate/adaptive immune stimulation. mRNA cancer vaccine precedes other conventional vaccine platforms due to high potency, safe administration, rapid development potentials, and cost-effective manufacturing. However, mRNA vaccine applications have been limited by instability, innate immunogenicity, and inefficient in vivo delivery. Appropriate mRNA structure modifications (i.e., codon optimizations, nucleotide modifications, self-amplifying mRNAs, etc.) and formulation methods (i.e., lipid nanoparticles (LNPs), polymers, peptides, etc.) have been investigated to overcome these issues. Tuning the administration routes and co-delivery of multiple mRNA vaccines with other immunotherapeutic agents (e.g., checkpoint inhibitors) have further boosted the host anti-tumor immunity and increased the likelihood of tumor cell eradication. With the recent U.S. Food and Drug Administration (FDA) approvals of LNP-loaded mRNA vaccines for the prevention of COVID-19 and the promising therapeutic outcomes of mRNA cancer vaccines achieved in several clinical trials against multiple aggressive solid tumors, we envision the rapid advancing of mRNA vaccines for cancer immunotherapy in the near future. This review provides a detailed overview of the recent progress and existing challenges of mRNA cancer vaccines and future considerations of applying mRNA vaccine for cancer immunotherapies.

Messenger RNA (mRNA) vaccine development for preventive and therapeutic applications has evolved rapidly over the last decade. The mRVNA vaccine has proven therapeutic efficacy in various applications, including infectious disease, immunotherapy, genetic disorders, regenerative medicine, and cancer. Many mRNA vaccines have made it to clinical trials, and a couple have obtained FDA approval. This emerging therapeutic approach has several advantages over conventional methods: safety; efficacy; adaptability; bulk production; and cost-effectiveness. However, it is worth mentioning that the delivery to the target site and in vivo degradation and thermal stability are boundaries that can alter their efficacy and outcomes. In this review, we shed light on different types of mRNA vaccines, their mode of action, and the process to optimize their development and overcome their limitations. We also have explored various delivery systems focusing on the nanoparticle-mediated delivery of the mRNA vaccine. Generally, the delivery system plays a vital role in enhancing mRNA vaccine stability, biocompatibility, and homing to the desired cells and tissues. In addition to their function as a delivery vehicle, they serve as a compartment that shields and protects the mRNA molecules against physical, chemical, and biological activities that can alter their efficiency. Finally, we focused on the future considerations that should be attained for safer and more efficient mRNA application underlining the advantages and disadvantages of the current mRNA vaccines.

Messenger RNA (mRNA) vaccines have emerged as a transformative platform in modern vaccinology. mRNA vaccine is a powerful alternative to traditional vaccines due to their high potency, safety, and efficacy, coupled with the ability for rapid clinical development, scalability and cost-effectiveness in manufacturing. Initially conceptualized in the 1970s, the first study about the effectiveness of a mRNA vaccine against influenza was conducted in 1993. Since then, the development of mRNA vaccines has rapidly gained significance, especially in combating the COVID-19 pandemic. Their unprecedented success during the COVID-19 pandemic, as demonstrated by the Pfizer-BioNTech and Moderna vaccines, highlighted their transformative potential. This review provides a comprehensive analysis of the mRNA vaccine technology, detailing the structure of the mRNA vaccine and its mechanism of action in inducing immunity. Advancements in nanotechnology, particularly lipid nanoparticles (LNPs) as delivery vehicles, have revolutionized the field. The manufacturing processes, including upstream production, downstream purification, and formulation are also reviewed. The clinical progress of mRNA vaccines targeting viruses causing infectious diseases is discussed, emphasizing their versatility and therapeutic potential. Despite their success, the mRNA vaccine platform faces several challenges, including improved stability to reduce dependence on cold chain logistics in transport, enhanced delivery mechanisms to target specific tissues or cells, and addressing the risk of rare adverse events. High costs associated with encapsulation in LNPs and the potential for unequal global access further complicate their widespread adoption. As the world continues to confront emerging viral threats, overcoming these challenges will be essential to fully harness the potential of mRNA vaccines. It is anticipated that mRNA vaccines will play a major role in defining and shaping the future of global health.

The development of messenger RNA (mRNA) and self-amplifying RNA (saRNA) vaccines has revolutionized modern vaccinology, particularly with the success of lipid nanoparticle (LNP)-based SARS-CoV-2 vaccines. Intranasal administration offers a promising approach for respiratory vaccines, providing mucosal immunity at the primary entry site of pathogens. However, the impact of different aerosolization delivery systems on RNA-LNP stability, recovery volume and functionality is not well understood. In this study, we compare the effects of three intranasal administration devices- a commercial Nebulizer, a commercial Spray, and a Laminar Fluid Ejection (LFE) Device developed by Rocket Science Health- on LNP physicochemical properties, RNA encapsulation efficiency, and functional protein expression level. Our findings demonstrate that high shear forces in the commercial nebulizer delivery system significantly increase LNP particle size (85 nm to 300 nm) and polydispersity index (PDI), leading to RNA degradation and reduced encapsulation efficiency (100–39%). Conversely, the LFE Device preserved LNP structural integrity, achieving the highest RNA encapsulation efficiency (94% for mRNA, 102% for saRNA) and superior functional protein expression (3-fold higher luciferase activity compared to the CM Nebulizer). These results highlight the importance of selecting an appropriate delivery system to optimize RNA-LNP delivery and retention in intranasal applications. Our study supports the LFE Device as a viable candidate for effective RNA-LNP-based mucosal vaccine administration, with potential applications in next-generation RNA therapeutics.

mRNA vaccines have shown great potential in responding to emerging infectious diseases, with their efficacy and stability largely dependent on the delivery vehicles—lipid nanoparticles (LNPs). This study aims to explore the mechanisms by which LNPs encapsulate mRNA, as well as the effects of different N/P ratios and acid types in nucleic acid solutions on the structure and properties of LNPs, using the ethanol solvent injection method as the encapsulation technique. Six systems were designed, based on the composition and proportions of the existing mRNA vaccine mRNA-1273, and molecular dynamics (MD) simulations were employed to investigate the self-assembly process of LNPs. Ethanol was used as a solvent instead of pure water to better mimic experimental conditions. The results indicate that lipid components self-assemble into nanoparticles under neutral conditions, with the ionizable lipid SM-102 predominantly concentrating in the core of the particles. Upon mixing with nucleic acids in acidic conditions, LNPs undergo disassembly, during which protonated SM-102 encapsulates mRNA through electrostatic interactions, forming stable hydrogen bonds. Cluster structure analysis revealed that the four lipid components of LNPs are distributed sequentially from the outside inwards as DMG-PEG 2000, DSPC, cholesterol, and protonated SM-102. Moreover, LNPs constructed under low pH or low N/P ratios using citric acid exhibited larger volumes and more uniform distribution. These findings provide a scientific basis for further designing and optimizing LNP components to enhance the efficacy of mRNA vaccine encapsulation.

In recent years, lipid nanoparticles (LNPs) have attracted extensive attention in tumor immunotherapy. Targeting immune cells in cancer therapy has become a strategy of great research interest. mRNA vaccines are a potential choice for tumor immunotherapy, due to their ability to directly encode antigen proteins and stimulate a strong immune response. However, the mode of delivery and lack of stability of mRNA are key issues limiting its application. LNPs are an excellent mRNA delivery carrier, and their structural stability and biocompatibility make them an effective means for delivering mRNA to specific targets. This study summarizes the research progress in LNP delivery carrier-assisted targeted controlled release mRNA vaccines in tumor immunity. The role of LNPs in improving mRNA stability, immunogenicity, and targeting is discussed. This review aims to systematically summarize the latest research progress in LNP delivery carrier-assisted targeted controlled release mRNA vaccines in tumor immunity to provide new ideas and strategies for tumor immunotherapy, as well as to provide more effective treatment plans for patients.

Lipid nanoparticles (LNPs) have emerged as a powerful non-viral carrier for drug delivery. With the prevalence of respiratory diseases, particularly highlighted by the current COVID-19 pandemic, investigations into applying LNPs to deliver inhaled therapeutics directly to the lungs are underway. The progress in LNP development as well as the recent pre-clinical studies in three main classes of inhaled encapsulated drugs: small molecules, nucleic acids and proteins/peptides will be discussed. The advantages of the pulmonary drug delivery system such as reducing systemic toxicity and enabling higher local drug concentration in the lungs are evaluated together with the challenges and design considerations for improved formulations. This review provides a perspective on the future prospects of LNP-mediated delivery of inhaled therapeutics for respiratory diseases.

We report a successful formulation of Artemisone (ATM) in transferrin (Tf)-conjugated nanostructured lipid carriers (NLCs), achieving nearly a five-times increase in cell toxicity. The escalating cost of new drug discoveries led to the repurposing of approved drugs for new indications. This study incorporated Artemisone, an antimalarial drug, into a nanostructured lipid carrier (NLC) and tested for possible anticancer effects. The aim was to develop NLCs, and transferrin-conjugated NLCs (NLC-Tf) encapsulating Artemisone to enhance its delivery and anticancer activity. NLC formulations were prepared using high-pressure homogenization followed by ultrasonication and were characterized by particle size, zeta potential, and PDI. The conjugation of (Tf) to (NLC) was confirmed using IR, and the anticancer activity was tested using MTS assay. All formulations were in the nanometer size range (140–167 nm) with different zeta potential values. IR spectroscopy confirmed the successful conjugation of transferrin to NLC. Upon testing the formulations on melanoma cell lines using MTS assay, there was a significant decrease in viability and an increase in the encapsulated ATM-Tf toxicity compared to positive control ATM. The NLCs presented a promising potential carrier for delivering ATM to melanoma cells, and further conjugation with Tf significantly improved the ATM cytotoxicity.

This study investigates a novel approach using spleen-targeting lipid nanoparticles (LNPs) to immunomodulate behavioral impairment in a Methyl-CpG-binding protein 2 (Mecp2) transgenic mouse model. In a human Mecp2 transgenic mouse model (B6. Mecp2 Tg1 ), spleen-targeting lipid nanoparticles encapsulated with antisense oligonucleotides (ASO) were employed as a mitigating agent. Splenic immune cells were analyzed using flow cytometry; autoantibody production was assessed using autoantigen protein microarrays, including a central nervous system (CNS) protein microarray. Furthermore, proinflammatory cytokines, MeCP2-mediated signaling pathways, and manifestations of behavior functions and kidney disease were examined. Our findings indicated a reduction in splenic MeCP2 levels following in vivo knockdown via ASO. Notably, splenic immune cells, including B and T cells, particularly plasma B cells, were significantly reduced after LNP-ASO treatment. Levels of autoantibodies against typical nuclear antigens such as Sm, U1-snRNP B/B, and nucleosome antigens, as well as brain antigens including OLIG2, GAD2, GJA1, and YWHAE, were significantly alleviated. Proinflammatory molecules such as IL-5, TNF-α, CCL20 and TGF-β1 showed significant reduction. Additionally, after the in vivo knockdown of MeCP2, levels of MeCP2 protein, phospho-CREB, and phospho-mTOR were reduced compared to the placebo group. A reduced IgG deposition in the brain of the B6. Mecp2 Tg1 mice were observed following treatment. Interestingly, behavioral functions and defects of the blood-brain barrier (BBB) were attenuated after spleen-targeted LNP-ASO treatment. Tissue-specific knockdown of a disease-promoting gene, MeCP2, via spleen-targeting LNPs effectively modulated the peripheral immune system resulting in subsequent amelioration of autoantibody production, inflammation, and behavioral deficits. These preclinical findings suggest that immunomodulation may be a promising therapeutic strategy for neuropsychiatric diseases.