MRNA-based therapeutics: powerful and versatile tools to combat diseases

mRNA therapeutics have revolutionized medicine, offering a versatile platform to address previously untreatable diseases. Recent advancements in biotechnology have enabled the efficient production of functional proteins, antibodies, and peptides via mRNA, providing rapid and adaptable solutions for vaccine development and therapeutic interventions. The success of mRNA vaccines, exemplified during the COVID-19 pandemic, underscores their potential for combating infectious diseases with unparalleled speed and scalability. This review explores the latest developments in mRNA technology, including innovations in design, delivery, and disease treatment; modulation of immune response; and the role of AI. Particular emphasis is placed on optimizing mRNA constructs to maximize therapeutic efficacy, new delivery vehicles for mRNA, and the modulations of immune response evoked by mRNA vaccines. The potential applications of mRNA therapeutics in genetic disorders, infectious diseases, and cancer are highlighted, alongside a discussion of existing challenges such as delivery efficiency and production scalability. By integrating molecular biology, RNA technology, and nanotechnology, mRNA therapeutics hold the promise of transforming precision medicine. These advancements offer hope for patients with complex or intractable conditions, paving the way for a new era in targeted therapies and personalized healthcare.

Messenger RNA (mRNA) vaccine technology has recently emerged as a revolutionary platform in modern immunology and vaccinology. Unlike conventional vaccines that rely on attenuated pathogens or protein subunits, mRNA vaccines deliver genetic instructions to host cells to produce antigenic proteins that trigger robust immune responses. The widespread success during the COVID-19 pandemic accelerated global interest in this platform. However, challenges such as mRNA instability, degradation by extracellular RNases, and delivery barriers still limit its broader application in other therapeutic areas. This review provides an in-depth analysis of current advancements in mRNA vaccine development, focusing on mRNA structure stabilization, innovative carrier systems, immunogenicity modulation, and potential clinical applications beyond infectious diseases. It also compares mRNA vaccines to traditional vaccine platforms and highlights their advantages and future prospects. A comprehensive literature survey was conducted using databases such as PubMed, Google Scholar, ScienceDirect, and Web of Science with keywords "mRNA vaccine", "lipid nanoparticles", "delivery systems", "immunogenicity", "cancer vaccines", "stability enhancement techniques", and "COVID-19". Research articles, clinical trial reports, patents, and review papers published between 2000 and 2025 were screened. Out of more than 300 publications, 126 relevant articles were selected based on novelty, scientific contribution, and relevance to vaccine development and delivery. The gathered information was critically organized and summarized. The review highlights formulation strategies such as nucleoside-modified mRNA, selfamplifying mRNA, and circular mRNA to enhance stability and translation efficiency. Delivery vectors including lipid nanoparticles (LNPs), polymeric nanoparticles, and lipid-polymer hybrids are discussed, emphasizing their role in protecting mRNA from degradation and enabling targeted delivery. In addition to infectious diseases, the use of mRNA vaccines for cancer immunotherapy and personalized medicine is examined. Clinical findings confirm high efficacy and potent immune responses, although reactogenicity and cold-chain dependence remain major limitations. This review offers a comprehensive overview of mRNA vaccine development and highlights key scientific innovations addressing the inherent challenges of mRNA instability and delivery. By comparing current delivery strategies and formulation methods, it provides valuable insights for researchers designing next-generation mRNA vaccines with improved safety, efficacy, and broader applicability. mRNA vaccines represent a transformative approach in vaccine science, with tremendous potential for rapid adaptation against emerging pathogens and personalized treatment strategies. Ongoing research aimed at improving thermostability, reducing adverse immune responses, and expanding disease coverage may further strengthen global acceptance of mRNA technology. Continued advances in delivery systems and regulatory approval frameworks will be essential for expanding its application across therapeutic domains.

Respiratory infectious diseases frequently erupt on a global scale, with RNA viruses, such as SARS‐CoV‐2, RSV, and influenza viruses, posing challenges to vaccine development due to their high mutation rates. Traditional vaccine development cycles are lengthy and struggle to keep pace with rapidly evolving viruses, whereas messenger RNA (mRNA) vaccines have demonstrated significant advantages due to their short development periods, straightforward production, and low costs. After the outbreak of the COVID‐19 pandemic, multiple mRNA vaccines, including Pfizer‐BioNTech and Moderna, rapidly received emergency use authorization, validating their feasibility. The Nobel Prize in Physiology or Medicine in 2023 was awarded to Katalin Karikó and Drew Weissman, underscoring the efficacy of mRNA vaccine technology. In 2024, the U.S. Food and Drug Administration (FDA) approval of Moderna's respiratory syncytial virus (RSV) mRNA vaccine marked the immense potential of mRNA technology in vaccine innovation. This review article summarizes the design, clinical research, and future challenges of mRNA vaccines for respiratory viruses, delving into antigen design, mRNA delivery systems, and advancements in vaccines for multiple respiratory viruses, including innovations in self‐amplifying mRNA and circular mRNA vaccines. Additionally, the development of combination vaccines is underway, aiming to provide protection against multiple viruses through a single administration. Despite the significant progress in mRNA vaccine development, challenges remain regarding raw material costs, stability, and delivery efficiency. In the future, with technological advancements and the accumulation of clinical experience, the design strategies and delivery systems of mRNA vaccines are expected to be continuously optimized, thereby enhancing their safety and efficacy.

Messenger RNA (mRNA) vaccines have quickly become a potent tool in cancer immunotherapy, with the potential to personalise cancer treatment and get around many of the drawbacks of conventional therapies. With an emphasis on their processes, technological developments, and clinical applications, this study examines the scientific breakthroughs and difficulties surrounding mRNA cancer vaccines. We begin by investigating the ways in which mRNA vaccines work to stimulate the immune system, encode antigens specific to tumours, and elicit a potent anti-tumor response. We also look at the variety of mRNA vaccines which are currently being deployed and emphasize their successes in clinical studies, especially when combined with immune checkpoint inhibitors. The effectiveness and safety of these vaccines have been significantly increased by technological developments, such as enhancements in mRNA stability, design, and delivery systems (such as lipid nanoparticles and polyplexes). Emerging technologies like circular RNA and self-amplifying present promising opportunities for enduring and more potent therapies. But there are still limitations with mRNA vaccines, such as stability, immunogenicity, degradation, and effective in vivo delivery. Concerns about possible adverse effects and safety in long-term applications are also covered in this review. Despite these obstacles, novel approaches are being developed to boost antigen expression, optimize delivery systems, and improve mRNA stability, establishing mRNA vaccines as a crucial component of tailored cancer immunotherapy. These developments provide the foundation for upcoming advances in mRNA vaccine technology and represent a major breakthrough in the fight against cancer.

Messenger RNA (mRNA) therapeutics have garnered considerable attention due to their remarkable efficacy in the treatment of various diseases. The COVID-19 mRNA vaccine and RSV mRNA vaccine have been approved on the market. Due to the inherent nuclease-instability and negative charge of mRNA, delivery systems are developed to protect the mRNA from degradation and facilitate its crossing cell membrane to express functional proteins or peptides in the cytoplasm. However, the deficiency in transfection efficiency and targeted biological distribution are still the major challenges for the mRNA delivery systems. In this review, we first described the physiological barriers in the process of mRNA delivery and then discussed the design approach and recent advances in mRNA delivery systems with an emphasis on their tissue/cell-targeted abilities. Finally, we pointed out the existing challenges and future directions with deep insights into the design of efficient mRNA delivery systems. We believe that a high-precision targeted delivery system can greatly improve the therapeutic effects and bio-safety of mRNA therapeutics and accelerate their clinical transformations. This review may provide a new direction for the design of mRNA delivery systems and serve as a useful guide for researchers who are looking for a suitable mRNA delivery system.

Targeted mRNA Therapy for Ornithine Transcarbamylase Deficiency.

Nanomaterials for Therapeutic RNA Delivery

Due to the fact that mRNA technology allows the production of diverse vaccines and treatments in a shorter time frame and with reduced expense compared to conventional approaches,there has been a surge in the use of mRNA-based therapeutics in recent years. With the aimof encoding tumour antigens for cancer vaccines, cytokines for immunotherapy, tumour suppressors to inhibit tumour development, chimeric antigen receptors for engineered T cell therapyor genome-editing proteins for gene therapy,many of these therapeutics have shown promising efficacy in preclinical studies, and some have evenentered clinical trials.Given the evidence supporting the effectiveness and safety of clinically approved mRNA vaccines, coupled with growing interest in mRNA-based therapeutics, mRNA technology is poised to become one of the major pillars in cancer drug development. In this Review, we present in vitro transcribed mRNA-based therapeutics for cancer treatment, including the characteristics of the various types of synthetic mRNA, the packaging systems for efficient mRNA delivery, preclinical and clinical studies, current challenges and future prospects in the field. We anticipate the translation of promising mRNA-based treatments into clinical applications, to ultimately benefit patients.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has facilitated the clinical implementation of messenger RNA (mRNA) vaccines. The successful development of lipid nanoparticles (LNPs)-based mRNA vaccines, such as Spikevax (Moderna) and...

An LNP-mRNA vaccine protects fish against rhabdovirus infection.

Optimizing mRNA translation efficiency through rational 5'UTR and 3'UTR combinatorial design.

The COVID-19 pandemic has spotlighted the potential of in vitro transcribed (IVT) mRNA vaccines with their demonstrated efficacy, safety, cost-effectiveness, and rapid manufacturing. Numerous IVT mRNA vaccines are now under clinical trials for a range of targets, including infectious diseases, cancers, and genetic disorders. Despite their promise, IVT mRNA vaccines face hurdles such as limited expression levels, nonspecific targeting beyond the liver, rapid degradation, and unintended immune activation. Overcoming these challenges is crucial to harnessing the full therapeutic potential of IVT mRNA vaccines for global health advancement. This review provides a comprehensive overview of the latest research progress and optimization strategies for IVT mRNA molecules and delivery systems, including the application of artificial intelligence (AI) models and deep learning techniques for IVT mRNA structure optimization and mRNA delivery formulation design. We also discuss recent development of the delivery platforms, such as lipid nanoparticles (LNPs), polymers, and exosomes, which aim to address challenges related to IVT mRNA protection, cellular uptake, and targeted delivery. Lastly, we offer insights into future directions for improving IVT mRNA vaccines, with the hope to spur further progress in IVT mRNA vaccine research and development.

The recent rapid advance in biotechnology has enabled the therapeutic use of messenger RNA (mRNA) to fight against a wide range of viral diseases and cancers. The development of mRNA vaccine and mRNA therapeutic agent showed extraordinary potential in safety, effica-cy, and industrial production. One of the most effective preventive measures against unex-pected, widespread outbreaks of infectious illnesses, like the pandemic coronavirus sickness that is presently raging, is the use of mRNA vaccines (COVID-19). It took decades for scien-tists to make the mRNA vaccine an applicable approach for medical use due to the stability and delivery of mRNA. Although the previous challenges were overcome, scientists still in-tended to further improve the stability, immunogenicity, delivery systems, and translation ef-ficiency of mRNA into the body to make mRNA technology even more powerful in both pre-ventative and therapeutic use. Encouraging results showed that the mRNA vaccine is a tre-mendous platform against infectious diseases and cancers, which is a new era in vaccinology and oncology. This study concentrated on a thorough overview of mRNA vaccine develop-ment, including a basic explanation of the mechanism of action of mRNA vaccines, various delivery techniques, present obstacles, and future prospects of mRNA vaccines for both pre-ventive and therapeutic purposes.

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 vaccines, boasting high potency, rapid development capabilities, cost-effectiveness, and safe administration. However, the clinical application of mRNA vaccines is hindered by the challenges of mRNA instability and inefficient in vivo delivery. In recent times, remarkable technological advancements have emerged to address these challenges, utilizing two main approaches: ex vivo transfection of dendritic cells (DCs) with mRNA and direct injection of mRNA-based therapeutics, either with or without a carrier. This review offers a comprehensive overview of major non-viral vectors employed for mRNA vaccine delivery. It showcases notable preclinical and clinical studies in the field of cancer immunotherapy and discusses important considerations for advancing these promising vaccine platforms for broader therapeutic applications. Additionally, we provide insights into future possibilities and the remaining challenges in mRNA delivery technology, emphasizing the significance of ongoing research in mRNA-based therapeutics.

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.