Archives of Science
Open Access

mRNA therapeutics; mRNA vaccines; cancer immunotherapy; genetic disorders; cardiovascular diseases; drug delivery systems; lipid nanoparticles; CRISPR/Cas; precision medicine; vaccine development

Introduction

mRNA therapeutics have dramatically shifted the medical landscape, particularly after their success in COVID-19 vaccines. This review explores the significant progress in mRNA delivery systems, stability, and translation efficiency. Beyond infectious diseases, these therapies are now being actively developed for cancer, genetic disorders, and autoimmune conditions, offering a versatile platform for precision medicine. The rapid adaptability and manufacturing scalability make them a promising avenue for future medical interventions[1].

mRNA vaccines are emerging as a powerful tool in cancer immunotherapy, moving beyond their well-known role in infectious diseases. This review highlights their potential to elicit robust and specific anti-tumor immune responses by delivering tumor-associated antigens or neoantigens. The flexibility of mRNA technology allows for rapid design and optimization, addressing the challenges of tumor heterogeneity and immunosuppressive microenvironments, making them a crucial area of development in oncology[2].

mRNA-based therapies offer a revolutionary approach to treating rare genetic diseases by providing instructions for the body to produce missing or defective proteins. This review highlights recent advances in improving mRNA stability, delivery, and translation efficiency. While facing challenges like transient expression and potential immunogenicity, the potential for personalized treatments and broad applicability across various monogenic disorders positions mRNA technology as a frontrunner in gene therapy[3].

The success of mRNA therapeutics heavily relies on efficient and safe delivery systems. This review delves into the latest advancements in carriers like lipid nanoparticles (LNPs), polymeric nanoparticles, and exosomes, which are crucial for protecting mRNA from degradation and facilitating cellular uptake. Optimizing these delivery platforms is key to enhancing therapeutic efficacy, minimizing off-target effects, and expanding the clinical applications of mRNA technology across various disease areas[4].

mRNA vaccines have revolutionized the approach to combating infectious diseases, as demonstrated by their rapid development and deployment during the COVID-19 pandemic. This article explains how these vaccines instruct host cells to produce pathogen-specific antigens, triggering potent and durable immune responses. The flexibility, speed of development, and high efficacy of mRNA technology make it an invaluable tool for global health security, enabling quick responses to emerging viral threats and persistent pathogens[5].

The mRNA vaccine platform has shown remarkable success, but its broader clinical application faces several challenges, including manufacturing scalability, cold chain requirements, and potential for off-target immune responses. This review discusses ongoing efforts to overcome these hurdles through improved mRNA design, novel delivery vehicles, and refined adjuvant strategies. Addressing these challenges will be critical for fully realizing the platform's potential in diverse therapeutic areas, from chronic diseases to personalized medicine[6].

Combining mRNA technology with CRISPR/Cas gene editing offers a transient, non-integrating approach to therapeutic genome modification, significantly reducing the risk of off-target effects. This article highlights the crucial role of efficient mRNA delivery systems for the Cas nuclease and guide RNA components. Recent progress in lipid nanoparticles and other delivery methods is enabling safer and more precise gene editing, opening new avenues for treating genetic disorders and even enhancing anti-cancer therapies[7].

mRNA-based cancer immunotherapy represents a dynamic and rapidly evolving field, leveraging the body's own machinery to produce tumor-specific antigens and stimulate robust anti-tumor immune responses. This review discusses the significant progress made in developing mRNA vaccines against various cancers, highlighting strategies to overcome challenges like tumor heterogeneity, immunosuppressive microenvironments, and ensuring effective delivery. It underscores the potential for personalized treatments and synergistic combinations to improve patient outcomes[8].

Achieving successful in vivo mRNA delivery is paramount for realizing the full therapeutic potential of this technology. This comprehensive review examines the current state and future directions of various delivery platforms, including lipid nanoparticles, polymeric systems, and viral vectors. It emphasizes the need for targeted delivery to specific cell types and tissues, along with strategies to minimize immunogenicity and maximize expression, thereby paving the way for more effective and safer systemic mRNA therapies[9].

While mRNA's success in vaccines is well-known, its therapeutic scope extends far beyond, particularly into chronic conditions like cardiovascular diseases. This review explores innovative mRNA strategies aimed at regenerating damaged heart tissue, delivering therapeutic proteins for conditions like heart failure, and revascularization. The transient nature of mRNA expression and its ability to deliver a wide array of protein-coding sequences make it a promising, flexible platform for addressing complex cardiovascular pathologies[10].

Description

mRNA therapeutics represent a significant evolution in medical science, profoundly changing the landscape of treatment, especially following their unprecedented success in COVID-19 vaccine development [1, 5]. This technology extends far beyond combating infectious diseases, actively exploring applications in cancer, genetic disorders, and autoimmune conditions. It offers a versatile platform for precision medicine, marked by its rapid adaptability, manufacturing scalability, and ability to trigger potent and durable immune responses against pathogen-specific antigens, making it an invaluable tool for global health security and quick responses to emerging viral threats [1, 5].

In the realm of oncology, mRNA vaccines are emerging as powerful tools for cancer immunotherapy [2, 8]. These therapies leverage the body's own cellular machinery to produce tumor-associated antigens or neoantigens, thereby stimulating robust and specific anti-tumor immune responses. The inherent flexibility of mRNA technology allows for rapid design and optimization, helping to address complex issues like tumor heterogeneity and the immunosuppressive microenvironments often found in cancers. This makes them a crucial area of development in oncology, holding considerable promise for personalized treatments and synergistic combinations to improve patient outcomes [2, 8].

For rare genetic diseases, mRNA-based therapies offer a revolutionary solution by providing direct instructions to the body to produce missing or defective proteins, thus addressing the underlying genetic causes [3]. Recent scientific advances have primarily focused on improving mRNA stability, optimizing delivery mechanisms, and enhancing translation efficiency. While these therapies face inherent challenges such as transient expression and potential immunogenicity, their broad applicability across various monogenic disorders and strong potential for personalized treatments position mRNA technology as a leading approach in gene therapy [3]. Furthermore, combining mRNA technology with CRISPR/Cas gene editing provides a transient, non-integrating method for therapeutic genome modification, significantly reducing risks of off-target effects [7]. The crucial role of efficient mRNA delivery systems for Cas nucleases and guide RNA components is recognized, with recent progress in lipid nanoparticles and other delivery methods enabling safer and more precise gene editing, opening new avenues for both genetic disorder treatment and enhanced anti-cancer therapies [7].

The overall success of mRNA therapeutics heavily relies on the development of efficient and safe delivery systems [4, 9]. These systems are absolutely essential for protecting fragile mRNA molecules from degradation within the body and for facilitating their efficient uptake into target cells. Significant advancements are continuously being made in various carriers, including lipid nanoparticles (LNPs), polymeric nanoparticles, and exosomes. Optimizing these sophisticated delivery platforms is critical for enhancing overall therapeutic efficacy, minimizing unwanted off-target effects, and broadening the clinical applications of mRNA technology across a wide array of disease areas. Achieving successful in vivo mRNA delivery is paramount, which necessitates targeted delivery to specific cell types and tissues, coupled with intelligent strategies to minimize immunogenicity and maximize expression, thereby paving the way for more effective and safer systemic mRNA therapies [4, 9].

Despite the remarkable progress and broad potential, the broader clinical application of the mRNA vaccine platform faces several complex challenges [6]. These hurdles include ensuring large-scale manufacturing scalability, meeting stringent cold chain requirements for storage and distribution, and mitigating the potential for off-target immune responses. Ongoing research and development efforts are intensely focused on overcoming these obstacles through continuous improvements in mRNA design, the creation of novel delivery vehicles, and refined adjuvant strategies [6]. Beyond its success in vaccines, the therapeutic scope of mRNA extends significantly into chronic conditions, notably cardiovascular diseases. Researchers are exploring innovative mRNA strategies aimed at regenerating damaged heart tissue, delivering vital therapeutic proteins for conditions such as heart failure, and promoting revascularization [10]. The transient nature of mRNA expression and its inherent ability to deliver a wide array of protein-coding sequences make it a promising and highly flexible platform for effectively addressing complex cardiovascular pathologies, ultimately pushing the boundaries of personalized medicine [6, 10].

Conclusion

mRNA therapeutics have fundamentally reshaped medicine, particularly since their groundbreaking success in COVID-19 vaccines. This versatile platform is rapidly expanding beyond infectious diseases to address significant health challenges like cancer, genetic disorders, autoimmune conditions, and cardiovascular diseases. Key areas of advancement include improving mRNA delivery systems, enhancing stability, and optimizing translation efficiency. These therapies offer the potential for precision medicine due to their rapid adaptability and manufacturing scalability, making them a promising avenue for future medical interventions. For cancer, mRNA vaccines are emerging as powerful tools in immunotherapy, designed to elicit strong anti-tumor immune responses by delivering tumor-associated antigens or neoantigens. The flexibility of this technology helps tackle tumor heterogeneity and immunosuppressive microenvironments. In rare genetic diseases, mRNA-based therapies offer a revolutionary path, guiding the body to produce missing or defective proteins. This approach faces challenges like transient expression and potential immunogenicity but holds great promise for personalized gene therapy. Efficient and safe delivery systems are vital for mRNA's success, with advancements in lipid nanoparticles, polymeric nanoparticles, and exosomes crucial for protecting mRNA and facilitating cellular uptake. Optimizing these platforms minimizes off-target effects and expands clinical applications. Furthermore, combining mRNA technology with CRISPR/Cas gene editing provides a transient, non-integrating method for genome modification, reducing off-target risks and opening new doors for treating genetic disorders and even enhancing anti-cancer therapies. While the mRNA platform shows remarkable success, challenges persist, including manufacturing scalability, cold chain logistics, and managing immune responses. Overcoming these hurdles through improved mRNA design, novel delivery, and refined adjuvant strategies is essential to realize its full therapeutic potential.

References

• Shaohui Q, Xiaofei T, Yuchen C (2023) mRNA therapeutics: moving from the COVID-19 pandemic to other diseases.Cell Res 33:279-291.

Indexed at, Google Scholar, Crossref

• Yuxin Z, Yue J, Yutong M (2023) mRNA vaccines in cancer immunotherapy: A review.Cell Mol Life Sci 80:161.

Indexed at, Google Scholar, Crossref

• Xin Z, Fengmei S, Yongjun L (2024) mRNA-based therapy for rare genetic diseases: advances, challenges, and perspectives.Signal Transduct Target Ther 9:181.

Indexed at, Google Scholar, Crossref

• Lin M, Ying Z, Haiyang Y (2023) Advanced mRNA delivery systems for therapeutic applications.Adv Drug Deliv Rev 196:114815.

Indexed at, Google Scholar, Crossref

• Norbert P, Michael JH, Frederick WP (2020) Messenger RNA Vaccines Against Infectious Diseases.Cold Spring Harb Perspect Biol 12:a038890.

Indexed at, Google Scholar, Crossref

• Yuqing H, Zhixin W, Heng G (2023) Current challenges and prospects of mRNA vaccine platform in clinical application.Int Immunopharmacol 119:110204.

Indexed at, Google Scholar, Crossref

• Amine PM, Robyn O, Jonas M (2023) Advances in mRNA delivery to cells for CRISPR/Cas applications.Mol Ther Nucleic Acids 32:579-599.

Indexed at, Google Scholar, Crossref

• Rui C, Yaqian S, Weijie L (2022) Messenger RNA-Based Cancer Immunotherapy: Progress and Challenges.Front Immunol 13:888631.

Indexed at, Google Scholar, Crossref

• Cong P, Ruan P, Yu C (2024) The future of in vivo mRNA delivery: advances and challenges.Signal Transduct Target Ther 9:180.

Indexed at, Google Scholar, Crossref

• Sara L, Emma L, Halil K (2024) Beyond vaccines: mRNA therapeutics for cardiovascular diseases.Mol Ther 32:994-1015.

Indexed at, Google Scholar, Crossref