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This book focuses on the fundamentals and applications of messenger RNA (mRNA)-based therapeutics and discusses the strengths and key challenges of this emerging class of drugs. In the past 30 years, extensive research and technological development in many areas have contributed to the emergence of in vitro transcribed mRNA as a therapeutic that has now reached clinical testing. Formulations that protect the mRNA from nucleases and accelerate its cellular uptake, combined with improvements to the mRNA molecules themselves, have been critical advancements for mRNAs to become viable therapeutics. Though once regarded as a serious impediment, the transient nature of mRNA technology is now considered a major advantage in making mRNA therapies safe and, ultimately, a potential game changer in the field of medicine. This new book in the RNA Technologies series provides a state-of-the-art overview on the emerging field of mRNA therapeutics covering essential strategies for formulation, delivery, and application. It also reviews the promising role in cancer immunotherapy, respiratory diseases, and chronic HBV infection and discusses RNA vaccines in light of the current COVID-19 pandemic. mRNA-based approaches have great potential to revolutionize molecular biology, cell biology, biomedical research, and medicine. Thus, this handbook is an essential resource for researchers in academia and industry contributing to the development of this new area of therapeutics.

This book offers a comprehensive and detailed overview of various aspects of long non-coding RNAs. It discusses their emerging significance in molecular medicine, ranging from human cancers to cardiovascular and metabolic diseases. Transcriptomic studies have demonstrated that the majority of genomes found in complex organisms are expressed in highly dynamic and cell-specific patterns, producing huge numbers of intergenic, antisense and intronic long non-protein-coding RNAs (lncRNAs). Thousands of lncRNAs have been identified, and unlike mRNA, they have no protein-coding capacity. A large repertoire of ncRNAs, actively transcribed from the mammalian genome, control diverse cellular processes, both in terms of development and diseases, through a variety of gene regulatory mechanisms. IncRNAs have emerged as a new paradigm in epigenetic regulation of the genome. Given its scope, the book will be of particular interest to molecular, chemical, cell and developmental biologists, as well as specialists in translational medicine involved in disease-oriented research. It also offers a valuable resource for in silico experts seeking a deeper understanding of lncRNA expression and function through computational analysis of the NGS data.

This book reviews the chemical, regulatory, and physiological mechanisms of protein arginine and lysine methyltransferases, as well as nucleic acid methylations and methylating enzymes. Protein and nucleic acid methylation play key and diverse roles in cellular signalling and regulating macromolecular cell functions.Protein arginine and lysine methyltransferases are the predominant enzymes that catalyse S-adenosylmethionine (SAM)-dependent methylation of protein substrates. These enzymes catalyse a nucleophilic substitution of a methyl group to an arginine or lysine side chain nitrogen (N) atom. Cells also have additional protein methyltransferases, which target other amino acids in peptidyl side chains or N-termini and C-termini, such as glutamate, glutamine, and histidine. All these protein methyltransferases use a similar mechanism. In contrast, nucleic acids (DNA and RNA) are substrates for methylating enzymes, which employ various chemical mechanisms to methylatenucleosides at nitrogen (N), oxygen (O), and carbon (C) atoms. This book illustrates how, thanks to there ability to expand their repertoire of functions to the modified substrates, protein and nucleic acid methylation processes play a key role in cells.

Many breakthroughs in experimental devices, advanced software, as well as analytical methods for systems biology development have helped shape the way we study DNA, RNA and proteins, on the genomic, transcriptional, translational and posttranslational level. This book highlights the comprehensive topics that encompass systems biology with enormous progress in the development of genome sequencing, proteomic and metabolomic methods in designing and understanding biological systems.Topics covered in this book include fundamentals of modelling networks, circuits and pathways, spatial and multi cellular systems, image-driven systems biology, evolution, noise and decision-making in single cells, systems biology of disease and immunology, and personalized medicine. Special attention is paid to epigenomics, in particular environmental conditions that impact genetic background. The breadth of exciting new data towards discovering fundamental principles and direct applicationof epigenetics in agriculture is also described.The chapter “Deciphering the Universe of RNA Structures and Trans RNA-RNA Interactions of Transcriptomes in vivo - from Experimental Protocols to Computational Analyses” is available open access under a CC BY 4.0 license via link.springer.com.

This book presents, in 26 chapters, the status quo in epigenomic profiling. It discusses how functional information can be indirectly inferred and describes the new approaches that promise functional answers, collectively referred to as epigenome editing. It highlights the latest important advances in our understanding of the functions of plant epigenomics and new technologies for the study of epigenomic marks and mechanisms in plants. Topics include the deposition or removal of chromatin modifications and histone variants, the role of epigenetics in development and response to environmental signals, natural variation and ecology, as well as applications for epigenetics in crop improvement. Discussing areas ranging from the complex regulation of stress and heterosis to the precise mechanisms of DNA and histone modifications, it presents breakthroughs in our understanding of complex phenotypic phenomena.

This volume is comprised of 18 chapters, covering various aspects of DNA modification and RNA modified bases. It also discusses in detail circular RNA, therapeutic oligonucleotides and their different properties. The chemical nature of DNA, RNA, protein and lipids makes these macromolecules easily modifiable, but they are also susceptible to damage from both endogenous and exogenous agents. Alkylation and oxidation show a potential to disrupt the cellular redox equilibrium and cause cellular damage leading to inflammation and even chronic disease. Furthermore, DNA damage can drive mutagenesis and the resulting DNA sequence changes can induce carcinogenesis and cancer progression. Modified nucleosides can occur as a result of oxidative DNA damage and RNA turnover, and are used as markers for various diseases. To function properly some RNA needs to be chemically modified post-transcriptionally. Dysregulation of the RNA-modification pattern or of the levelsof the enzymes that catalyze these modifications alters RNA functionality and can result in complex phenotypes, likely due to defects in protein translation. While modifications are best characterized in noncoding ribonucleic acids like tRNA and rRNA, coding mRNAs have also been found to contain modified nucleosides. This book is a valuable resource, not only for graduate students but also researchers in the fields of molecular medicine and molecular biology.

The aim of molecular diagnostics is preferentially to detect a developing disease before any symptoms appear. There has been a significant increase, fueled by technologies from the human genome project, in the availability of nucleic acid sequence information for all living organisms including bacteria and viruses. When combined with a different type of instrumentation applied, the resulting diagnostics is specific and sensitive. Nucleic acid-based medical diagnosis detects specific DNAs or RNAs from the infecting organism or virus and a specific gene or the expression of a gene associated with a disease. Nucleic acid approaches also stimulate a basic science by opening lines of inquiry that will lead to greater understanding of the molecules at the center of life. One can follow Richard Feynman's famous statement “What I cannot create, I do not understand.”