Tumor is a complex disease that seriously threatens human health. Traditional treatment methods have many limitations. In recent years, with the in-depth study of tumor immune mechanisms, the mRNA vaccine, as an innovative immunotherapy strategy, has attracted wide attention due to its unique advantages and great potential. The purpose of this review is to introduce the technical development status of tumor mRNA vaccines, the application progress in a variety of tumors, and the challenges and future development directions, to provide reference for related research. In this paper, we reviewed the recent literature on tumor mRNA vaccines, analyzed the technical progress in structure modification, delivery tools, immunogenicity regulation, and summarized its application in different tumor types, and discussed the current challenges and future development directions. Conclusions: Remarkable progress has been made in structural modification, delivery tool optimization, and immunogenicity regulation of tumor mRNA vaccines, which show good application prospects in the treatment of a variety of tumors. However, the complexity of the tumor microenvironment, the limitation of immune activation, the stability and translation efficiency of mRNA, and the optimization of delivery systems are still challenges. In the future, the application of new technologies, the exploration of combined treatment strategies, and the advancement of personalized medicine will provide new opportunities for the development of tumor mRNA vaccines. With the continuous progress of technology, tumor mRNA vaccines are expected to play an important role in tumor treatment and bring greater well-being to human health.

Since the beginning of the COVID-19 pandemic, the development of messenger RNA (mRNA) vaccines has made significant progress in the pharmaceutical industry. The two COVID-19 mRNA vaccines from Moderna and Pfizer/BioNTech have been approved for marketing and have made significant contributions to preventing the spread of SARS-CoV-2. In addition, mRNA therapy has brought hope to some diseases that do not have specific treatment methods or are difficult to treat, such as the Zika virus and influenza virus infections, as well as the prevention and treatment of tumors. With the rapid development of in vitro transcription (IVT) technology, delivery systems, and adjuvants, mRNA therapy has also been applied to hereditary diseases such as Fabry's disease. This article reviews the recent development of mRNA vaccines for structural modification, treatment and prevention of different diseases; delivery carriers and adjuvants; and routes of administration to promote the clinical application of mRNA therapies.

Messenger RNA (mRNA) vaccines have emerged as one of the most promising and rapidly evolving immunotherapeutic approaches due to their ease of production, demonstrated clinical efficacy, and high safety. The coronavirus disease 2019(COVID-19) pandemic has showcased the remarkable therapeutic potential of mRNA vaccines, prompting researchers to explore their use for cancer treatment. Preclinical studies and human clinical trials have indicated their substantial clinical applicability. However, current research faces several challenges, including the complexity of tumor antigen selection, vaccine stability, and the development of resistance. This review summarizes the optimization strategies for cancer mRNA vaccines in preclinical settings, the progress of clinical trials, and the challenges encountered while analyzing various delivery vehicle types, infusion methods, and application cases across different cancer types, highlighting key factors in vaccine design. The findings demonstrate that mRNA vaccines elicit specific immune responses and exhibit favorable safety and tolerability in clinical trials. Moreover, developing personalized neoantigen vaccines offers a novel direction for cancer immunotherapy. The unique contribution of this review lies in its comprehensive overview of the latest advancements in therapeutic mRNA vaccines for cancer treatment while identifying critical areas for future research to propel the field forward.

Tumor-derived total RNA (TdRNA) vaccines induce broad immune responses by either synthesizing tumor-specific antigens or activating pattern recognition receptors, making them a promising tool in cancer immunotherapy for the activation of cytotoxic T lymphocytes (CTLs). However, TdRNA vaccines face issues such as low stability and inadequate immune activation. To overcome these challenges, we have developed a dissolvable microneedle delivery platform, PTC NVs@MNs, designed for the simultaneous delivery of TdRNA and CpG oligodeoxynucleotides (CpG ODN). This platform stabilizes TdRNA, maintaining its activity for up to 30 days at room temperature and promotes dendritic cell maturation, and then activates T lymphocyte-mediated antitumor immunity through the targeted delivery of TdRNA and CpG. PTC NVs@MNs not only enhance dendritic cell maturation and increase CD8+ T cell infiltration into tumors, eliciting robust antitumor immune responses that inhibit tumor growth, but also induce antitumor immune memory to prevent tumor development. This innovative approach offers therapeutic and preventive benefits in tumor management. STATEMENT OF SIGNIFICANCE: Tumor-derived total RNA (TdRNA) holds potential for eliciting a broad immune response; however, its therapeutic efficacy against triple-negative breast cancer (TNBC) is constrained by low stability and inadequate immune activation. To overcome these limitations, we engineered a dissolving microneedle patch for transdermal co-delivery of TdRNA and CpG oligodeoxynucleotides (CpG ODN). This system not only stabilizes TdRNA-maintaining its bioactivity for 30 days at room temperature-but also promotes dendritic cell maturation and activates T lymphocyte-mediated antitumor immunity . This study demonstrated that the well-designed microneedle patch effectively prevents RNA degradation without requiring stringent storage conditions, offering both therapeutic and preventive benefits in tumor management.

Over the past 20 years, intensive research has been conducted on the development of therapeutic mRNA, leading to numerous discoveries that have enabled its use in therapy. The main achievements in this field include increasing mRNA stability, reducing its immunogenicity (i.e., its ability to trigger an immune response), and solving the challenge of delivering mRNA into cells-all to achieve a therapeutic effect. The aim of this study was to review the scientific literature on the use of mRNA technology in the production of vaccines. Various methods of applying mRNA technology that could potentially be introduced into clinical practice in the future are described. A detailed analysis was conducted on the approved COVID-19 vaccines developed by Pfizer/BioNTech (New York, NY, USA) and Moderna (Kirkland, QC, Canada), as their introduction marked a groundbreaking moment in the advancement of mRNA technology. This study was based on the latest scientific literature from reputable publishers and medical databases such as PubMed and ClinicalTrials. In conclusion, mRNA technology is currently experiencing rapid development, significantly driven by the ongoing COVID-19 pandemic. The application of this technology holds great potential not only for vaccines against infectious diseases but also for cancer treatment. However, further research is necessary to facilitate its broader clinical implementation.

Non-coding RNAs (ncRNAs) are a class of RNAs that largely lack the capacity to encode proteins. They have garnered significant attention due to their central regulatory functions across numerous cellular and physiological processes at transcriptional, post-transcriptional, and translational levels. Over the past decade, ncRNA-based therapies have gained considerable attention in the diagnosis, treatment, and prevention of diseases, and many studies have revealed a significant relationship between ncRNAs and diseases. At the same time, due to their tissue specificity, an increasing number of projects have focused on the application of ncRNAs as biomarkers in diseases, as well as the design and development of novel ncRNA-based vaccines and therapies for clinical use. These ncRNAs may also drive research into the potential molecular mechanisms and complex pathogenesis of related diseases. However, new biomarkers need to be validated for their clinical effectiveness. Additionally, to produce safe and stable RNA products, factors such as purity, precise dosage, and effective delivery methods must be ensured to achieve optimal bioactivity. These challenges remain key issues in the clinical application of ncRNAs. This review summarizes the prospects of ncRNAs as potential biomarkers, as well as the current research status and clinical applications of ncRNAs in therapies and vaccines, and discusses the challenges and expectations of ncRNAs in disease diagnosis and drug therapy.

Immunotherapy has surfaced as a promising therapeutic modality for gastric cancer (GC). A comprehensive review of advancements, current status, and research trends in GC immunotherapy is essential to inform future investigative efforts.

To delineate the trends, advancements, and focal points in immunotherapy for GC.

We performed a bibliometric analysis of 2906 articles in English concerning GC immunotherapy published from 2000 to December 20, 2023, indexed in the Web of Science Core Collection. Data analysis and visualization were facilitated by CiteSpace (6.1.6R), VOSviewer v.1.6.17, and GraphPad Prism v8.0.2.

There has been an increase in the annual publication rate of GC immunotherapy research. China leads in publication volume, while the United States demonstrates the highest citation impact. Fudan University is notable for its citation frequency and publication output. Co-citation analysis and keyword frequency revealed and highlighted a focus on GC prognosis, the tumor microenvironment (TME), and integrative immunotherapy with targeted therapy. Emerging research areas include gastroesophageal junction cancer, adoptive immunotherapy, and the role of Treg cell in immunotherapy.

GC immunotherapy research is an expanding field attracting considerable scientific interest. With the clinical adoption of immunotherapy in GC, the primary goals are to enhance treatment efficacy and patient outcomes. Unlike hematological malignancies, GC's solid TME presents distinct immunological challenges that may attenuate the cytotoxic effects of immune cells on cancer cells. For instance, although CAR-T therapy is effective in hematological malignancies, it has underperformed in GC settings. Current research is centered on overcoming immunosuppression within the TME, with a focus on combinations of targeted therapy, adoptive immunotherapy, Treg cell dynamics, and precise prognosis prediction in immunotherapy. Additionally, immunotherapy's role in treating gastroesophageal junction cancer has become a novel research focus.

The prevalence of multidrug-resistant (MDR) ESKAPE pathogens, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, represents a critical global public health challenge. In response, mRNA vaccines offer an adaptable and scalable platform for immunotherapy against ESKAPE pathogens by encoding specific antigens that stimulate B-cell-driven antibody production and CD8+ T-cell-mediated cytotoxicity, effectively neutralizing these pathogens and combating resistance. This review examines recent advancements and ongoing challenges in the development of mRNA vaccines targeting MDR ESKAPE pathogens. We explore antigen selection, the nuances of mRNA vaccine technology, and the complex interactions between bacterial infections and antibiotic resistance. By assessing the potential efficacy of mRNA vaccines and addressing key barriers to their paraclinical implementation, this review highlights the promising function of mRNA-based immunization in combating MDR ESKAPE pathogens.

Immunotherapy is an established and efficient treatment strategy for a variety of malignancies. It aims to boost the anticancer properties of one's own immune system. Several immunotherapeutic options are available, but immune checkpoint blockers represent the most widely known and investigated. Anticancer vaccines represent an evolving area of immunotherapy that stimulate antigen-presenting cells, cytotoxic responses of CD8+ T cells, and the presence of memory T cells, among others. Over the years, different approaches for anticancer vaccines have been studied, such as mRNA and DNA vaccines, together with dendritic cell- and viral vector-based vaccines. Recently, an accumulating number of clinical studies have been performed to analyze the safety and potential efficacy of these agents. The aim of this review is to summarize recent advances regarding different types of therapeutic anticancer vaccines. Furthermore, it will discuss how recent advances in preclinical models can enhance clinical outcomes.

Background: Recent advances in mRNA vaccine technology, accelerated by the global COVID-19 pandemic, have generated significant interest in their applications beyond infectious diseases. Dentistry has emerged as a promising field for exploring the potential of mRNA-based therapies in preventing and treating oral diseases. Objectives: This narrative review aims to evaluate the current status of mRNA vaccine development and its preclinical applications in oral health, focusing on periodontal disease, dental caries, regenerative medicine, implantology, and oral cancer. Methods: The review synthesizes findings from preclinical studies, including research conducted in animal models and in vitro, to assess the potential of mRNA-based therapies to modulate immune responses and promote tissue regeneration in the oral cavity. Clinical trials were only mentioned in the context of broader areas of mRNA vaccine implementation such as oncology and immunotherapy. Results: The preclinical studies highlight the capacity of mRNA vaccines to enhance the body's immune response and facilitate tissue repair processes. Despite these promising results, challenges persist in delivering mRNA vaccines effectively within the complex oral environment. These challenges include vaccine stability, delivery mechanisms, and the modulation of immune responses. Conclusions: While mRNA vaccines offer significant promise for revolutionizing oral health care, they face notable limitations concerning safety, efficacy, and clinical feasibility. Overcoming these obstacles through further research is essential to unlock their full translational potential and ensure their safe and effective integration into dental practice.

Melanoma, an aggressive skin cancer, presents significant therapeutic challenges. Consequently, innovative treatment strategies beyond conventional chemotherapy, radiation, and surgery are actively explored. This review discusses the evolution of immunotherapy in advanced melanoma, highlighting PD-1/PD-L1 inhibitors, mRNA vaccines, Talimogene Laherparepvec (T-VEC), and tumor-infiltrating lymphocyte (TIL) therapies. PD-1/PD-L1 inhibitors such as pembrolizumab and nivolumab block immune checkpoints, promoting T-cell cytotoxic activity and improving overall survival in patients with advanced melanoma. T-VEC, a modified oncolytic herpes virus, promotes a systemic anti-tumor response while simultaneously lysing malignant cells. mRNA vaccines, such as Moderna's mRNA-4157/V940, take advantage of malignant-cell-specific neoantigens to amplify the adaptive immune response while protecting healthy tissue. TIL therapy is a form of therapy involving ex vivo expansion and reinfusion of the patient's tumor-specific lymphocytes and has been shown to provide durable tumor control. While these therapies have demonstrated promising clinical outcomes, challenges such as tumor resistance, high financial burden, and limited accessibility pose challenges to their widespread use. This review explores combination therapies such as PD-L1 inhibitors with mRNA vaccines, or TIL therapy, which aim to enhance treatment through synergistic approaches. Further research is required to optimize these combinations, address barriers preventing their use, and control adverse events.

We evaluated the possible application of RNA-cleaving deoxyribozymes to control the number and size of cleavage products obtained during the mid-down characterization of larger nucleic acids by mass spectrometry (MS). We assessed the structural determinants of substrate selectivity, as well as the effects of cofactor, additives, and environmental parameters on the cleavage activity of the histidine-dependent deoxyribozyme 3 (HD3). We designed dedicated sets of HD3 variants capable of cleaving RNA strands as large as the 758 nt enhanced green fluorescent protein (eGFP) mRNA. This substrate was dissected into only 10 oligonucleotides with lengths ranging from 46 to 120 nt, which compared favorably with the 87 unique products ranging from 3 to 14 nt to be expected instead from putative RNase T1 digestion. The complexity of such mixture was sufficiently limited to enable its comprehensive analysis by direct infusion nanospray-MS without front-end separation. Their unambiguous assignment was accomplished by matching experimental with predicted masses, which revealed the formation of mis-cleaved products and enabled the mass mapping of 100% of the initial substrate. Product identity was verified by collision-induced dissociation (CID), which provided individual sequence coverages ranging from 87 to 100%, with the lower figure obtained from a 120 nt mis-cleaved product. All sequence information combined accounted for 95% coverage of the 758 nt substrate, but without all the ambiguities engendered by classic nucleotide-specific endonucleases. This outcome demonstrated the feasibility of mid-down approaches based on deoxyribozymes and underscored their potential in the analysis of larger RNAs.

Nucleic acid vaccines have emerged as crucial advancements in vaccine technology, particularly highlighted by the global response to the COVID-19 pandemic. The widespread administration of mRNA vaccines against COVID-19 to billions globally marks a significant milestone. Furthermore, the approval of an mRNA vaccine for Respiratory Syncytial Virus (RSV) this year underscores the versatility of this technology. In oncology, the combination of mRNA vaccine encoding neoantigens and immune checkpoint inhibitors (ICIs) has shown remarkable efficacy in eliciting protective responses against diseases like melanoma and pancreatic cancer. Although the use of a COVID-19 DNA vaccine has been limited to India, the inherent stability at room temperature and cost-effectiveness of DNA vaccines present a viable option that could benefit developing countries. These advantages may help DNA vaccines address some of the challenges associated with mRNA vaccines. Currently, several trials are exploring the use of DNA-encoded neoantigens in combination with ICIs across various cancer types. These studies highlight the promising role of nucleic acid-based vaccines as the next generation of immunotherapeutic agents in cancer treatment. This review will delve into the recent advancements and current developmental status of both mRNA and DNA-based cancer vaccines.

Immuno-oncology has witnessed remarkable advancements in the past decade, revolutionizing the landscape of cancer therapeutics in an encouraging manner. Among the diverse immunotherapy strategies, mRNA vaccines have ushered in a new era for the therapeutic management of malignant diseases, primarily due to their impressive impact on the COVID-19 pandemic. In this comprehensive review, we offer a systematic overview of mRNA vaccines, focusing on the optimization of structural design, the crucial role of delivery materials, and the administration route. Additionally, we summarize preclinical studies and clinical trials to provide valuable insights into the current status of mRNA vaccines in cancer treatment. Furthermore, we delve into a systematic discussion on the significant challenges facing the current development of mRNA tumor vaccines. These challenges encompass both intrinsic and external factors that are closely intertwined with the successful application of this innovative approach. To pave the way for a more promising future in cancer treatments, a deeper understanding of immunological mechanisms, an increasing number of high-quality clinical trials, and a well-established manufacturing platform are crucial. Collaborative efforts between scientists, clinicians, and industry engineers are essential to achieving these goals.

Cancer continues to be a leading factor in mortality and tackling it has been made difficult by the development of immune escape. Furthermore, alternative treatments like surgery, chemotherapy, and radiation have been unsuccessful in eradicating cancer. Despite being effective, they have not succeeded in providing a full cancer treatment and exhibit several negative effects. The field of immunotherapy has been improved by utilizing cancer vaccines, immune checkpoint inhibitors (ICIs), and adoptive cell transfer to enhance immune responses to tumors. Nevertheless, cancer cells need to adapt and become immune to immune reactions, leading to the need for innovative treatment methods. Carbohydrate polymers and their nanoparticles have been beneficial in improving cancer immunotherapy by being customizable to specifically target the immune system. These nanoparticles can change the tumor microenvironment and accelerate immunotherapy by affecting immune cells such as T cells and dendritic cells. Incorporating both chemotherapy and phototherapy into nanoparticles can improve immunotherapy. Furthermore, besides controlling immune reactions, carbohydrate polymer nanoparticles can also be used for theranostic purposes, where they are used to image tumor cells and activate the immune system to eradicate cancer.

In recent years, infectious diseases like COVID-19 have had profound global socio-economic impacts. mRNA vaccines have gained prominence due to their rapid development, industrial adaptability, simplicity, and responsiveness to new variants. Notably, the 2023 Nobel Prize in Physiology or Medicine recognized significant contributions to mRNA vaccine research.

Our study employed a comprehensive bibliometric analysis using the Web of Science Core Collection (WoSCC) database, encompassing 5,512 papers on mRNA vaccines from 2003 to 2023. We generated cooperation maps, co-citation analyses, and keyword clustering to evaluate the field's developmental history and achievements.

The analysis yielded knowledge maps highlighting countries/institutions, influential authors, frequently published and highly cited journals, and seminal references. Ongoing research hotspots encompass immune responses, stability enhancement, applications in cancer prevention and treatment, and combating infectious diseases using mRNA technology.

mRNA vaccines represent a transformative development in infectious disease prevention. This study provides insights into the field's growth and identifies key research priorities, facilitating advancements in vaccine technology and addressing future challenges.

The research and development of messenger RNA (mRNA) cancer vaccines have gradually overcome numerous challenges through the application of personalized cancer antigens, structural optimization of mRNA, and the development of alternative RNA-based vectors and efficient targeted delivery vectors. Clinical trials are currently underway for various cancer vaccines that encode tumor-associated antigens (TAAs), tumor-specific antigens (TSAs), or immunomodulators. In this paper, we summarize the optimization of mRNA and the emergence of RNA-based expression vectors in cancer vaccines. We begin by reviewing the advancement and utilization of state-of-the-art targeted lipid nanoparticles (LNPs), followed by presenting the primary classifications and clinical applications of mRNA cancer vaccines. Collectively, mRNA vaccines are emerging as a central focus in cancer immunotherapy, offering the potential to address multiple challenges in cancer treatment, either as standalone therapies or in combination with current cancer treatments.

Neoantigen, unique peptides resulting from tumor-specific mutations, represent a promising frontier in oncology for personalized cancer immunotherapy. Their unique features allow for the development of highly specific and effective cancer treatments, which can potentially overcome the limitations of conventional therapies. This paper explores the current prospects and challenges associated with the application of neoantigens in oncology. We examine the latest advances in neoantigen identification, vaccine development, and adoptive T cell therapy. Additionally, we discuss the obstacles related to neoantigen heterogeneity, immunogenicity prediction, and the tumor microenvironment. Through a comprehensive analysis of current research and clinical trials, this paper aims to provide a detailed overview of how neoantigens could revolutionize cancer treatment and the hurdles that must be overcome to realize their full potential.

In the ongoing quest for new treatments in medicine, traditional Chinese medicine offers unique insights and potential. Recently, studies on the ability of Calculus bovis to inhibit M2-type tumour-associated macrophage polarisation by modulating the Wnt/β-catenin signalling pathway to suppress liver cancer have undoubtedly revealed new benefits and hope for this field of research. The purpose of this article is to comment on this study and explore its strengths and weaknesses, thereby providing ideas for the future treatment of liver cancer.

Harnessing the power of the immune system to target cancer cells is one of the most appealing approaches for cancer therapy. Among these immunotherapies, messenger ribonucleic acid (mRNA) cancer vaccines are worthy of consideration, as they have demonstrated promising results in clinical trials. These vaccines have proven to be safe and well-tolerated. They can be easily mass-produced in a relatively short time and induce a systemic immune response effective against both the primary tumor and metastases. Transcripts encoding immunomodulatory molecules can also be incorporated into the mRNA, enhancing its efficacy. On the other hand, there are some challenges associated with their application, including mRNA instability, insufficient uptake by immune cells, and intrinsic immunogenicity, which can block mRNA translation. Many innovations have been suggested to overcome these obstacles, including structural modification (such as 5' cap modification), optimizing delivery vehicles (especially dendritic cells (DCs) and nanoparticles), and using antigens that can enhance immunogenicity by circumventing tolerance mechanisms. A popular approach is to combine mRNA cancer vaccines with traditional and novel cancer treatments like chemotherapy, radiotherapy, and immune checkpoint blockade (ICB). They are most efficacious when combined with other therapies like ICBs. There is still a long way to go before these vaccines enter the standard of care for cancer patients, but with the incredible pace of development in this field, their clinical application will soon be witnessed. This review highlights the recent advances and challenges of mRNA cancer vaccines. Finally, some of the most prominent clinical applications of these vaccines will be reviewed.

Compared to other types of tumor vaccines, RNA vaccines have emerged as promising alternatives to conventional vaccine therapy due to their high efficiency, rapid development capability, and potential for low-cost manufacturing and safe drug delivery. RNA vaccines mainly include mRNA, circular RNA (circRNA), and Self-amplifying mRNA(SAM). Different RNA vaccine platforms for different tumors have shown encouraging results in animal and human models. This review comprehensively describes the advances and applications of RNA vaccines in antitumor therapy. Future directions for extending this promising vaccine platform to a wide range of therapeutic uses are also discussed.

Messenger RNA (mRNA) therapeutics have been widely employed as strategies for the treatment and prevention of diseases. Amid the global outbreak of COVID-19, mRNA vaccines have witnessed rapid development. Generally, in the case of mRNA vaccines, the initiation of the innate immune system serves as a prerequisite for triggering subsequent adaptive immune responses. Critical cells, cytokines, and chemokines within the innate immune system play crucial and beneficial roles in coordinating tailored immune reactions towards mRNA vaccines. Furthermore, immunostimulators and delivery systems play a significant role in augmenting the immune potency of mRNA vaccines. In this comprehensive review, we systematically delineate the latest advancements in mRNA vaccine research, present an in-depth exploration of strategies aimed at amplifying the immune effectiveness of mRNA vaccines, and offer some perspectives and recommendations regarding the future advancements in mRNA vaccine development.

Originally devised for cancer control, mRNA vaccines have risen to the forefront of medicine as effective instruments for control of infectious disease, notably their pivotal role in combating the COVID-19 pandemic. This review focuses on fundamental aspects of the development of mRNA vaccines, e.g., tumor antigens, vector design, and precise delivery methodologies, - highlighting key technological advances. The recent, promising success of personalized mRNA vaccines against pancreatic cancer and melanoma illustrates the potential value for other intractable, immunologically resistant, solid tumors, such as glioblastoma, as well as the potential for synergies with a combinatorial, immunotherapeutic approach. The impact and progress in human cancer, including pancreatic cancer, head and neck cancer, bladder cancer are reviewed, as are lessons learned from first-in-human CAR-T cell, DNA and dendritic cell vaccines targeting glioblastoma. Going forward, a roadmap is provided for the transformative potential of mRNA vaccines to advance cancer immunotherapy, with a particular focus on the opportunities and challenges of glioblastoma. The current landscape of glioblastoma immunotherapy and gene therapy is reviewed with an eye to combinatorial approaches harnessing RNA science. Preliminary preclinical and clinical data supports the concept that mRNA vaccines could be a viable, novel approach to prolong survival in patients with glioblastoma.

Head and neck cancer (HNC) is a highly aggressive type of tumor characterized by delayed diagnosis, recurrence, metastasis, relapse, and drug resistance. The occurrence of HNC were associated with smoking, alcohol abuse (or both), human papillomavirus infection, and complex genetic and epigenetic predisposition. Currently, surgery and radiotherapy are the standard treatments for most patients with early-stage HNC. For recurrent or metastatic (R/M) HNC, the first-line treatment is platinum-based chemotherapy combined with the antiepidermal growth factor receptor drug cetuximab, when resurgery and radiation therapy are not an option. However, curing HNC remains challenging, especially in cases with metastasis. In this review, we summarize the pathogenesis of HNC, including genetic and epigenetic changes, abnormal signaling pathways, and immune regulation mechanisms, along with all potential therapeutic strategies such as molecular targeted therapy, immunotherapy, gene therapy, epigenetic modifications, and combination therapies. Recent preclinical and clinical studies that may offer therapeutic strategies for future research on HNC are also discussed. Additionally, new targets and treatment methods, including antibody-drug conjugates, photodynamic therapy, radionuclide therapy, and mRNA vaccines, have shown promising results in clinical trials, offering new prospects for the treatment of HNC.

Malignant tumors remain a primary cause of human mortality. Among the various treatment modalities for neoplasms, tumor vaccines have consistently shown efficacy and promising potential. These vaccines offer advantages such as specificity, safety, and tolerability, with mRNA vaccines representing promising platforms. By introducing exogenous mRNAs encoding antigens into somatic cells and subsequently synthesizing antigens through gene expression systems, mRNA vaccines can effectively induce immune responses. Katalin Karikó and Drew Weissman were awarded the 2023 Nobel Prize in Physiology or Medicine for their great contributions to mRNA vaccine research. Compared with traditional tumor vaccines, mRNA vaccines have several advantages, including rapid preparation, reduced contamination, nonintegrability, and high biodegradability. Tumor-targeted therapy is an innovative treatment modality that enables precise targeting of tumor cells, minimizes damage to normal tissues, is safe at high doses, and demonstrates great efficacy. Currently, targeted therapy has become an important treatment option for malignant tumors. The application of mRNA vaccines in tumor-targeted therapy is expanding, with numerous clinical trials underway. We systematically outline the targeted delivery mechanism of mRNA vaccines and the mechanism by which mRNA vaccines induce anti-tumor immune responses, describe the current research and clinical applications of mRNA vaccines in tumor-targeted therapy, and forecast the future development trends of mRNA vaccine application in tumor-targeted therapy.

Cancer immunotherapy has sparked a wave of cancer research, driven by recent successful proof-of-concept clinical trials. However, barriers are emerging during its rapid development, including broad adverse effects, a lack of reliable biomarkers, tumor relapses, and drug resistance. Integration of nanomedicine may ameliorate current cancer immunotherapy. Ultra-large surface-to-volume ratio, extremely small size, and easy modification surface of nanoparticles enable them to selectively detect cells and kill cancer cells in vivo. Exciting synergistic applications of the two approaches have emerged in treating various cancers at the intersection of cancer immunotherapy and cancer nanomedicine, indicating the potential that the combination of these two therapeutic modalities can lead to new paradigms in the treatment of cancer. This review discusses the status of current immunotherapy and explores the possible opportunities that the nanomedicine platform can make cancer immunotherapy more powerful and precise by synergizing the two approaches.

mRNA vaccines are regarded as a highly promising avenue for next-generation cancer therapy. Nevertheless, the intricacy of production, inherent instability, and low expression persistence of linear mRNA significantly restrict their extensive utilization. Circular RNAs (circRNAs) offer a novel solution to these limitations due to their efficient protein expression ability, which can be rapidly generated in vitro without the need for extra modifications. Here, we present a novel neoantigen vaccine based on circRNA that induces a potent anti-tumor immune response by expressing hepatocellular carcinoma-specific tumor neoantigens. By cyclizing linearRNA molecules, we were able to enhance the stability of RNA vaccines and form highly stable circRNA molecules with the capacity for sustained protein expression. We confirmed that neoantigen-encoded circRNA can promote dendritic cell (DC) activation and enhance DC-induced T-cell activation in vitro, thereby enhancing T-cell killing of tumor cells. Encapsulating neoantigen-encoded circRNA within lipid nanoparticles for in vivo expression has enabled the creation of a novel circRNA vaccine platform. This platform demonstrates superior tumor treatment and prevention in various murine tumor models, eliciting a robust T-cell immune response. Our circRNA neoantigen vaccine offers new options and application prospects for neoantigen immunotherapy in solid tumors.

Due to the outbreak of novel coronavirus pneumonia, messenger RNA (mRNA) technology has attracted heated attention. A specific, safe, and efficient mRNA delivery system is needed. Lipid nanocarriers have become attractive carriers for mRNA delivery due to their high delivery efficiency, few side effects, and easy modification to change their structures and functions. To achieve the desired biological effect, lipid nanocarriers must reach the designated location for effective drug delivery. Therefore, the effects of the composition of lipid nanocarriers on their key properties are briefly reviewed. In addition, the progress of smart drug delivery by changing the composition of lipid nanocarriers is summarized, and the importance of component design and structure is emphasized. Subsequently, this review summarizes the latest progress in lipid nanocarrier-based mRNA technology and provides corresponding strategies for its current challenges, putting forward valuable information for the future design of lipid nanocarriers and mRNA.

Therapeutic mRNA vaccines have become powerful therapeutic tools for severe diseases, including infectious diseases and malignant neoplasms. mRNA vaccines encoding tumor-associated antigens provide unprecedented hope for many immunotherapies that have hit the bottleneck. However, the application of mRNA vaccines is limited because of biological instability, innate immunogenicity, and ineffective delivery in vivo. This study aims to construct a novel mRNA vaccine delivery nanosystem to successfully co-deliver a tumor-associated antigen (TAA) encoded by the Wilms' tumor 1 (WT1) mRNA. In this system, named PSB@Nb1.33C/mRNA, photosynthetic bacteria (PSB) efficiently delivers the iMXene-WT1 mRNA to the core tumor region using photo-driven and hypoxia-driven properties. The excellent photothermal therapeutic (PTT) properties of PSB and 2D iMxene (Nb1.33C) trigger tumor immunogenic cell death, which boosts the release of the WT1 mRNA. The released WT1 mRNA is translated, presenting the TAA and amplifying immune effect in vivo. The designed therapeutic strategy demonstrates an excellent ability to inhibit distant tumors and counteract postsurgical lung metastasis. Thus, this study provides an innovative and effective paradigm for tumor immunotherapy, i.e., photo-immunogene cancer therapy, and establishes an efficient delivery platform for mRNA vaccines, thereby opening a new path for the wide application of mRNA vaccines.

Colorectal cancer (CRC) is a typical cancer that accounts for 10% of all new cancer cases annually and nearly 10% of all cancer deaths. Despite significant progress in current classical interventions for CRC, these traditional strategies could be invasive and with numerous adverse effects. The poor prognosis of CRC patients highlights the evident and pressing need for more efficient and targeted treatment. Novel strategies regarding mRNA vaccines for anti-tumor therapy have also been well-developed since the successful application for the prevention of COVID-19. mRNA vaccine technology won the 2023 Nobel Prize in Physiology or Medicine, signaling a new direction in human anti-cancer treatment: mRNA medicine. As a promising new immunotherapy in CRC and other multiple cancer treatments, the mRNA vaccine has higher specificity, better efficacy, and fewer side effects than traditional strategies. The present review outlines the basics of mRNA vaccines and their advantages over other vaccines and informs an available strategy for developing efficient mRNA vaccines for CRC precise treatment. In the future, more exploration of mRNA vaccines for CRC shall be attached, fostering innovation to address existing limitations.

Gene therapies have emerged as promising treatments for various conditions including inherited diseases as well as cancer. Ensuring their safe clinical application requires the development of appropriate safety testing strategies. Several guidelines have been provided by health authorities to address these concerns. These guidelines state that non-clinical testing should be carried out on a case-by-case basis depending on the modality. This review focuses on the genome safety assessment of frequently used gene therapy modalities, namely Adeno Associated Viruses (AAVs), Lentiviruses, designer nucleases and mRNAs. Important safety considerations for these modalities, amongst others, are vector integrations into the patient genome (insertional mutagenesis) and off-target editing. Taking into account the constraints of in vivo studies, health authorities endorse the development of novel approach methodologies (NAMs), which are innovative in vitro strategies for genotoxicity testing. This review provides an overview of NAMs applied to viral and CRISPR/Cas9 safety, including next generation sequencing-based methods for integration site analysis and off-target editing. Additionally, NAMs to evaluate the oncogenicity risk arising from unwanted genomic modifications are discussed. Thus, a range of promising techniques are available to support the safe development of gene therapies. Thorough validation, comparisons and correlations with clinical outcomes are essential to identify the most reliable safety testing strategies. By providing a comprehensive overview of these NAMs, this review aims to contribute to a better understanding of the genome safety perspectives of gene therapies.

Messenger RNA (mRNA) based vaccines were instrumental in accelerating the end of the SARS-CoV-2 pandemic and are being aggressively developed as prophylaxes for a range of viral diseases. The swift adoption of mRNA-based therapeutics has also left open vast areas of opportunity for improving the development of mRNA-based drugs. One such area with immense potential focuses on the mRNA drug substance production, where mRNA is generated by a cell-free reaction called in vitro transcription (IVT). Process analytical technologies (PAT) are integral to the pharmaceutical industry and are necessary to facilitate agile process optimization and enhance process quality, control, and understanding. Due to the complexity and novelty inherent to the IVT reaction, there is a need for effective PAT that would provide in-depth, real-time insight into the reaction process to allow delivery of novel mRNA vaccines to patients faster in a more cost-effective way. Herein, we showcase the development of flow-nuclear magnetic resonance (flow-NMR) as a highly effective process-analytical tool for monitoring mRNA IVT reactions to support process development, optimization, and production.

Messenger RNA (mRNA)-based therapeutic strategies have shown remarkable promise in preventing and treating a staggering range of diseases. Optimizing the structure and delivery system of engineered mRNA has greatly improved its stability, immunogenicity, and protein expression levels, which has led to a wider range of uses for mRNA therapeutics. Herein, a thorough analysis of the optimization strategies used in the structure of mRNA is first provided and delivery systems are described in great detail. Furthermore, the latest advancements in biomedical engineering for mRNA technology, including its applications in combatting infectious diseases, treating cancer, providing protein replacement therapy, conducting gene editing, and more, are summarized. Lastly, a perspective on forthcoming challenges and prospects concerning the advancement of mRNA therapeutics is offered. Despite these challenges, mRNA-based therapeutics remain promising, with the potential to revolutionize disease treatment and contribute to significant advancements in the biomedical field.

Recent advances in mRNA technology and its delivery have enabled mRNA-based therapeutics to enter a new era in medicine. The rapid, potent, and transient nature of mRNA-encoded proteins, without the need to enter the nucleus or the risk of genomic integration, makes them desirable tools for treatment of a range of diseases, from infectious diseases to cancer and monogenic disorders. The rapid pace and ease of mass-scale manufacturability of mRNA-based therapeutics supported the global response to the COVID-19 pandemic. Nonetheless, challenges remain with regards to mRNA stability, duration of expression, delivery efficiency, and targetability, to broaden the applicability of mRNA therapeutics beyond COVID-19 vaccines. By learning from the rapidly expanding preclinical and clinical studies, we can optimise the mRNA platform to meet the clinical needs of each disease. Here, we will summarise the recent advances in mRNA technology; its use in vaccines, immunotherapeutics, protein replacement therapy, and genomic editing; and its delivery to desired specific cell types and organs for development of a new generation of targeted mRNA-based therapeutics.

mRNA-based vaccines are emerging as a promising alternative to standard cancer treatments and the conventional vaccines. Moreover, the FDA-approval of three nucleic acid based therapeutics (Onpattro, BNT162b2 and mRNA-1273) has further increased the interest and trust on this type of therapeutics. In order to achieve a significant therapeutic efficacy, the mRNA needs from a drug delivery system. In the last years, several delivery platforms have been explored, being the lipid nanoparticles (LNPs) the most well characterized and studied. A better understanding on how mRNA-based therapeutics operate (both the mRNA itself and the drug delivery system) will help to further improve their efficacy and safety. In this review, we will provide an overview of what mRNA cancer vaccines are and their mode of action and we will highlight the advantages and challenges of the different delivery platforms that are under investigation.

The design of an RNA sequence v that encodes an input target protein sequence w is a crucial aspect of messenger RNA (mRNA) vaccine development. There are an exponential number of possible RNA sequences for a single target protein due to codon degeneracy. These potential RNA sequences can assume various secondary structure conformations, each with distinct minimum free energy (MFE), impacting thermodynamic stability and mRNA half-life. Furthermore, the presence of species-specific codon usage bias, quantified by the codon adaptation index (CAI), plays a vital role in translation efficiency. While earlier studies focused on optimizing either MFE or CAI, recent research has underscored the advantages of simultaneously optimizing both objectives. However, optimizing one objective comes at the expense of the other. In this work, we present the Pareto Optimal RNA Design problem, aiming to identify the set of Pareto optimal solutions for which no alternative solutions exist that exhibit better MFE and CAI values. Our algorithm DEsign RNA (DERNA) uses the weighted sum method to enumerate the Pareto front by optimizing convex combinations of both objectives. We use dynamic programming to solve each convex combination in O ( | w | 3 ) time and O ( | w | 2 ) space. Compared with a CDSfold, previous approach that only optimizes MFE, we show on a benchmark data set that DERNA obtains solutions with identical MFE but superior CAI. Moreover, we show that DERNA matches the performance in terms of solution quality of LinearDesign, a recent approach that similarly seeks to balance MFE and CAI. We conclude by demonstrating our method's potential for mRNA vaccine design for the SARS-CoV-2 spike protein.

RNA-based therapies have catalyzed a revolutionary transformation in the biomedical landscape, offering unprecedented potential in disease prevention and treatment. However, despite their remarkable achievements, these therapies encounter substantial challenges including low stability, susceptibility to degradation by nucleases, and a prominent negative charge, thereby hindering further development. Chemically modified platforms have emerged as a strategic innovation, focusing on precise alterations either on the RNA moieties or their associated delivery vectors. This comprehensive review delves into these platforms, underscoring their significance in augmenting the performance and translational prospects of RNA-based therapeutics. It encompasses an in-depth analysis of various chemically modified delivery platforms that have been instrumental in propelling RNA therapeutics toward clinical utility. Moreover, the review scrutinizes the rationale behind diverse chemical modification techniques aiming at optimizing the therapeutic efficacy of RNA molecules, thereby facilitating robust disease management. Recent empirical studies corroborating the efficacy enhancement of RNA therapeutics through chemical modifications are highlighted. Conclusively, we offer profound insights into the transformative impact of chemical modifications on RNA drugs and delineates prospective trajectories for their future development and clinical integration.

The past decade has witnessed significant advances in the systemic treatment of advanced hepatocellular carcinoma (HCC). Nevertheless, the newly developed treatment strategies have not achieved universal success and HCC patients frequently exhibit therapeutic resistance to these therapies. Precision treatment represents a paradigm shift in cancer treatment in recent years. This approach utilizes the unique molecular characteristics of individual patient to personalize treatment modalities, aiming to maximize therapeutic efficacy while minimizing side effects. Although precision treatment has shown significant success in multiple cancer types, its application in HCC remains in its infancy. In this review, we discuss key aspects of precision treatment in HCC, including therapeutic biomarkers, molecular classifications, and the heterogeneity of the tumor microenvironment. We also propose future directions, ranging from revolutionizing current treatment methodologies to personalizing therapy through functional assays, which will accelerate the next phase of advancements in this area.

Despite being a new promising tool for cancer therapy, intravenous delivery of oncolytic viruses (OVs) is greatly limited by poor tumor targeting, rapid clearance in the blood, severe organ toxicity, and cytokine release syndrome. Herein, a simple and efficient strategy of erythrocyte-leveraged oncolytic virotherapy (ELeOVt) is reported, which for the first time assembled OVs on the surface of erythrocytes with up to near 100% efficiency and allowed targeted delivery of OVs to the lung after intravenous injection to achieve excellent treatment of pulmonary metastases while greatly improving the biocompatibility of OVs as a drug. Polyethyleneimine (PEI) as a bridge to assemble OVs on erythrocytes also played an important role in promoting the transfection of OVs. It is found that ELeOVt approach significantly prolonged the circulation time of OVs and increased the OVs distribution in the lung by more than tenfold, thereby significantly improving the treatment of lung metastases while reducing organ and systemic toxicity. Taken together, these findings suggest that the ELeOVt provides a biocompatible, efficient, and widely available approach to empower OVs to combat lung metastasis.

RNA therapeutics is a biological term regarding the usage of RNA-based molecules for medical purposes. Thanks to the success of mRNA-vaccine production against COVID-19, RNA therapeutics has gained more and more attention and investigation from worldwide scientists. It is considered as one of the promising alternatives for conventional drugs. In this first chapter, we presented an overview of the history and perspectives of RNA therapeutics' development. This chapter also explained the underlying mechanisms of different RNA-based molecules, including antisense oligonucleotide, interfering RNA (iRNA), aptamer, and mRNA, from degrading mRNA to inactivating targeted protein. Although there are many advantages of RNA therapeutics, its challenges in designing RNA chemical structure and the delivery vehicle need to be discussed. We described advanced technologies in the development of drug delivery systems that are positively correlated to the efficacy of the drug. Our aim is to provide a general background of RNA therapeutics to the audience before introducing plenty of more detailed parts, including clinical applications in certain diseases in the following chapters of the "RNA therapeutics" book.

RNA therapeutics are a class of drugs that use RNA molecules to treat diseases, including cancer. RNA therapeutics work by targeting specific genes or proteins involved in the disease process, with the aim of blocking or altering their activity to ultimately halt or reverse the disease progression. The use of RNA therapeutics in cancer treatment has shown great potential, as they offer the ability to specifically target cancer cells while leaving healthy cells intact. This is in contrast to traditional chemotherapy and radiation treatments, which can damage healthy cells and cause unpleasant side effects. The field of RNA therapeutics is rapidly advancing, with several types of RNA molecules being developed for cancer treatment, including small interfering RNA, microRNA, mRNA, and RNA aptamers. Each type of RNA molecule has unique properties and mechanisms of action, allowing for targeted and personalized cancer treatments. In this chapter, we will explore the different types of RNA therapeutics used in cancer treatment, their mechanisms of action, and their potential applications in treating different types of cancer. We will also discuss the challenges and opportunities in the development and research of RNA therapeutics for cancer, as well as the future outlook for this promising field.