ABSTRACT
Nucleic acids, as a next generation of biotechnology drugs, not only can fundamentally treat diseases, but also own significant platform characteristics in view of technology and production. Therefore, nucleic acid-based drugs have broad clinical applications in biomedical fields. However, nucleic acids are degradable and unstable, and have very low intracellular delivery efficiency in vitro and in vivo, which greatly limits their applications. In recent years, ionizable lipid-based lipid nanoparticles have shown promising application potentials and have been successfully applied to COVID-19 (Coronavirus Disease 2019) vaccines in clinic. Lipid nanoparticles demonstrate high in vivo delivery efficiency and good safety profile due to their unique structural and physicochemical properties, which provides many possibilities for their clinical applications for nucleic acid delivery in the future. This review focused on the characteristics of nucleic acid drugs and their delivery barriers, and discussed the approved nucleic acid drugs to illustrate the key aspects of the success of their delivery carrier system. In addition, problems to be solved in the field were highlighted.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.
ABSTRACT
Nucleic acids, as a next generation of biotechnology drugs, not only can fundamentally treat diseases, but also own significant platform characteristics in view of technology and production. Therefore, nucleic acid-based drugs have broad clinical applications in biomedical fields. However, nucleic acids are degradable and unstable, and have very low intracellular delivery efficiency in vitro and in vivo, which greatly limits their applications. In recent years, ionizable lipid-based lipid nanoparticles have shown promising application potentials and have been successfully applied to COVID-19 (Coronavirus Disease 2019) vaccines in clinic. Lipid nanoparticles demonstrate high in vivo delivery efficiency and good safety profile due to their unique structural and physicochemical properties, which provides many possibilities for their clinical applications for nucleic acid delivery in the future. This review focused on the characteristics of nucleic acid drugs and their delivery barriers, and discussed the approved nucleic acid drugs to illustrate the key aspects of the success of their delivery carrier system. In addition, problems to be solved in the field were highlighted.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.
ABSTRACT
Last decade has witnessed tremendous growth in the new promising treatment options based on mRNA, RNAi, antisense RNA, and RNA aptamers, the four classes of RNA-based therapeutics. Among these, mRNA-based therapy is centered on producing proteins within the cells to supplant deficient or abnormal proteins and in vaccination to a target pathogen. The potential of mRNA therapeutics is evident from the two major mRNA vaccines approved for COVID-19: developed by Moderna and by Pfizer. Nonetheless, mRNA therapeutic potential extends far beyond this, such as in treating genetic diseases, cancers, and other infectious diseases. Given the potential of mRNA therapeutics, this chapter is written to provide the reader an insight into the features of several synthetic mRNA platforms, production, purification;strategies to increase the stability and reduce the immunogenicity of therapeutic mRNA molecules;delivery methods of these mRNAs in vivo;and their applications, safety, and efficacy. Graphical : A detailed diagram of the chemically modified mRNA, with the in vitro delivery modes on the left, and the myriad of applications, namely the treatment of major genetic diseases on the right. The IVT mRNA is represented with more details above the diagram. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.
ABSTRACT
Messenger RNA (mRNA) vaccines have been studied for decades, but only recently, during the COVID-19 pandemic, has the technology garnered noteworthy attention. In contrast to traditional vaccines, mRNA vaccines elicit a more balanced immune response, triggering both humoral and cellular components of the adaptive immune system. However, some inherent hurdles associated with stability, immunogenicity, in vivo delivery, along with the novelty of the technology, have generated scepticism in the adoption of mRNA vaccines. Recent developments have pushed to bypass these issues and the approval of mRNA-based vaccines to combat COVID-19 has further highlighted the feasibility, safety, efficacy, and rapid development potential of this platform, thereby pushing it to the forefront of emerging therapeutics. This review aims to demystify mRNA vaccines, delineating the evolution of the technology which has emerged as a timely solution to COVID-19 and exploring the immense potential it offers as a prophylactic option for other cryptic diseases.
Subject(s)
COVID-19 , Pandemics , COVID-19/prevention & control , Humans , Pandemics/prevention & control , RNA, Messenger/genetics , Vaccines, Synthetic/genetics , mRNA VaccinesABSTRACT
RNA can alter the expression of endogenous genes and can be used to express therapeutic proteins. As a result, RNA-based therapies have recently mitigated disease in patients. Yet most potential RNA therapies cannot currently be developed, in large part because delivering therapeutic quantities of RNA drugs to diseased cells remains difficult. Here, recent studies focused on the biological hurdles that make in vivo drug delivery challenging are described. Then RNA drugs that have overcome these challenges in humans, focusing on siRNA to treat liver disease and mRNA to vaccinate against COVID, are discussed. Finally, research centered on improving drug delivery to new tissues is highlighted, including the development of high-throughput in vivo nanoparticle DNA barcoding assays capable of testing over 100 distinct nanoparticles in a single animal.