As our understanding of immune mediated chronic inflammatory diseases (IMIDs) grows, it becomes more and more clear that these conditions result from the convergence of a multitude of pathogenic mechanisms whose relative individual contribution is different in different patient subsets. Promising new technologies have been conceived that address the hypotheses that targeting multiple pathways simultaneously, selectively delivering therapeutics to areas of inflammation and/or resetting the immune system, could take efficacy to new levels. However, we have long waited for the arrival of some of these technologies to the bedside, or even far enough in the drug development process in spite of the initial enthusiasm. Some of the examples covered in this book include bispecific antibodies and genomic medicines, microparticles and targeted delivery of drugs to inflamed vasculature. Most published reviews and book chapters on novel therapies for inflammatory diseases describe positive attributes of molecules or technologies under investigation and the rationale for developing them into therapeutics. The originality and potential value of this book is not in the description of these targets or technologies from the point of view of their structure or mechanism of action exclusively, but rather, in making an effort to critically address the question of what is needed to move these technologies into the clinic. Has the technology not made it past the preclinical stage and why? Has it already been tested in humans and failed? What are the potential reasons behind those failures? What do experts in each field believe can be done better to increase the probabilities of success? In addition, the authors address the competitive landscape and summarize clinical studies that have failed in the respective area. They talk about the patient populations that would be required for the successful conduction of a clinical trial to test certain molecules, and they proactively share their views regarding both the potential and the drawbacks of targets or methodologies.

Autoimmune diseases are diverse and responsible for considerable morbidity. Their etiology remains largely unknown, and current therapy with anti-inflammatory drugs is prone to adverse effects, and rarely curative. New therapies with anti-cytokine antibodies or receptors are promising, but require frequent administration of expensive protein drugs. Gene Therapy of Autoimmune Diseases comprehensively reviews research in gene therapy for autoimmune diseases with viral or non-viral vectors. Gene therapy offers the possibility of long-term, continuous delivery of a wide variety of immunosuppressive, anti-inflammatory, or tolerance-inducing agents. Moreover, highly specific genetically modified cells can be produced. This book discusses the most promising avenues in this exciting new field.

Modern healthcare faces a significant challenge, namely that 25-70% of patients with common diseases do not benefit from standard treatments despite the availability of over 13,000 drugs registered in DrugBank. This discrepancy is likely due to these diseases' complex and heterogeneous molecular nature rather than a lack of therapeutic options. Emerging technologies have revealed the immense molecular complexity underlying common diseases. For instance, singlecell RNA sequencing (scRNA-seq) has demonstrated altered gene interactions in and across multiple cell types in numerous tissues. Furthermore, these technologies have revealed vast molecular differences between patients with the same diagnosis. There is a wide gap between this complexity and the current diagnostic and therapeutic approaches. Aim: To bring personalized medicine one step closer to the clinic; this thesis focuses on developing digital disease models that can capture the molecular biological complexity of disease in individual patients. We aim to harness these disease models to identify optimal treatments for each individual patient. Paper I: We started by exploring the usefulness of OMIC-based approaches for diagnostic and therapeutic predictions. Utilizing a single-cell RNA-sequenced mouse model of antigen-induced arthritis, we aimed to prioritize cell types and therapeutic targets. Initial pathway enrichment analyses did not yield relevant prioritization, prompting an investigation into network-based approaches. Multi-cellular disease models (MCDMs) for AIA and human rheumatoid arthritis were constructed, incorporating predicted cell type interactions. Centrality analysis indicated that these interactions could quantify a cell type’s relative importance in disease pathogenesis. We hypothesized that transcriptomic alterations in central cell types might reflect the MCDM, serving as potential diagnostic markers. An analysis of CD4+ T cells from patients with 13 different inflammatory diseases and healthy controls demonstrated that these profiles could discriminate between healthy and diseased states and among diseases. Furthermore, a network-based approach identified drugs targeting disease- associated changes common to multiple inflammatory diseases. Notably, one of these drugs, bezafibrate, successfully dampened inflammation in the AIA mouse model. Paper II: Building on the insights from Paper I, we investigated multicellular network models (MNMs) with time as an additional dimension. Using seasonal allergic rhinitis (SAR) as a disease model, we analyzed time-series scRNAseq data to construct MNMs of inflammatory diseases. We identified thousands of disease-associated expression changes across multiple cell types, varying at different disease stages. Notably, upstream regulators (URs) of these changes were also stage-dependent and multidirectional. To prioritize URs for drug discovery, we focused on those causing significant expression changes in multiple cell types across all time points. This strategy was validated through similar analyses of atopic dermatitis, ulcerative colitis, and Crohn’s disease, confirming that ranked URs aligned with the efficacy of existing drugs targeting the URs in the respective diseases. Furthermore, experimental validation included targeting the top-ranked regulatory gene in SAR, which was more effective than previously discovered IL4 inhibition. Paper III: While Paper I established the use of transcriptomic data for therapeutic predictions, it focused on overlapping disease-related changes across multiple inflammatory diseases and considered transcriptomic changes in only one cell type. Paper II indicated a potential benefit in UR prioritization in numerous cell types. However, it yielded heterogeneous results and was limited by the fact that few drugs directly target URs. Neither of these approaches was feasible for individualized drug predictions. Drawing on previous insights by us and others, we next aimed to develop digital disease models for individual patients, termed digital twins, with the capability for drug efficacy screening. We proposed scDrugPrio, a strategy utilizing single-cell scRNA-sequencing-based multicellular disease models incorporating key biological and pharmacological properties, such as varying gene expression levels, varying gene interactions within and between cell types, and drug effect. scDrugPrio was constructed based on a mouse model of arthritis and validated by improved precision/recall for known drugs and in vitro studies of predicted drugs that were FDA approved for other diseases and had not yet been tried in rheumatoid arthritis or mouse arthritis. For validation, scDrugPrio was applied to human multiple sclerosis as well as Crohn’s disease data that included tissue samples from healthy and sick tissue of all patients; scDrugPrio was able to identify relevant treatments for individual patients and could distinguish anti-TNF responders from non-responders. Conclusion: This thesis demonstrates a framework for constructing digital disease models for personalized therapeutic predictions that might hold potential for better clinical treatment decisions. By leveraging advanced genome-wide analyses and network-based approaches, we may enhance the precision and efficacy of treatments for immune-mediated inflammatory diseases, bringing personalized medicine closer to clinical reality.

Over the past decade the world has seen the rise of the fascinating and diverse field currently recognized as nanotechnology. This book covers a broad spectrum of topics within nanotechnology, including synthesis techniques, various innovative characterization techniques, growth mechanisms of nanomaterials, the physics and chemistry of nanomaterials, diverse functionalization methods, and the various applications of nanomaterials in biology, therapeutics, energy, food science, and environmental science. It also discusses applications of nanostructured materials, integrative applications such as nano- and micro-electronic sensor devices, as well as agricultural and environmental remediation applications. The book also includes a discussion of advances in functionalized nanomaterials (0D, 1D, 2D and 3D) and covers the early stages of the development of functionalized nanostructures, considering the future for 2D nanomaterials and 3D objects. Additionally, it includes a chapter on nanomaterial research development that highlights work on the life-cycle analysis of nanostructured materials and toxicity aspects. This book proves useful for researchers and professionals working in the field of nanomaterials and green technology, as well as in the field of nanotechnology. It should be useful to students and specialized researchers in a number of disciplines ranging from biology, chemistry, and materials science to engineering and manufacturing in both academia and industry.

Humans coexist with millions of harmless microorganisms, but emerging diseases, resistance to antibiotics, and the threat of bioterrorism are forcing scientists to look for new ways to confront the microbes that do pose a danger. This report identifies innovative approaches to the development of antimicrobial drugs and vaccines based on a greater understanding of how the human immune system interacts with both good and bad microbes. The report concludes that the development of a single superdrug to fight all infectious agents is unrealistic.

This new series, based on a bi-annual conference and its topics, represents a major contribution to the emerging science of cancer research and regenerative medicine. Each volume brings together some of the most pre-eminent scientists working on cancer biology, cancer treatment, cancer diagnosis, cancer prevention and regenerative medicine to share information on currently ongoing work which will help shape future therapies. These volumes are invaluable resources not only for already active researchers or clinicians but also for those entering these fields, plus those in industry. Tissue Engineering and Regenerative Medicine is a proceedings volume which reflects papers presented at the 3rd bi-annual Innovations in Regenerative Medicine and Cancer Research conference; taken with its companion volume Stem Cells: Biology and Engineering it provides a complete overview of the papers from that meeting of international experts.

With a history that likely dates back to the dawn of human civilization more than 10,000 years ago, and a record that includes the domestication and selective breeding of plants and animals, the harnessing of fermentation process for bread, cheese, and brewage production, and the development of vaccines against infectious diseases, biotechnology has acquired a molecular focus during the 20th century, particularly following the resolution of DNA double helix in 1953, and the publication of DNA cloning protocol in 1973, and transformed our concepts and practices in disease diagnosis, treatment and prevention, pharmaceutical and industrial manufacturing, animal and plant industry, and food processing. While molecular biotechnology offers unlimited opportunities for improving human health and well-being, animal welfare, agricultural innovation and environmental conservation, a dearth of high quality books that have the clarity of laboratory manuals without distractive procedural details and the thoroughness of well-conversed textbooks appears to dampen the enthusiasm of aspiring students. In attempt to fill this glaring gap, Handbook of Molecular Biotechnology includes four sections, with the first three presenting in-depth coverage on DNA, RNA and protein technologies, and the fourth highlighting their utility in biotechnology. Recognizing the importance of logical reasoning and experimental verification over direct observation and simple description in biotechnological research and development, the Introduction provides pertinent discussions on key strategies (i.e., be first, be better, and be different), effective thinking (lateral, parallel, causal, reverse, and random), and experimental execution, which have proven invaluable in helping advance research projects, evaluate and prepare research reports, and enhance other scientific endeavors. Key features Presents state-of-the-art reviews on DNA, RNA and protein technologies and their biotechnological applications Discusses key strategies, effective thinking, and experimental execution for scientific research and development Fills the gap left by detailed-ridden laboratory manuals and insight-lacking standard textbooks Includes expert contributions from international scientists at the forefront of molecular biotechnology research and development Written by international scientists at the forefront of molecular biotechnology research and development, chapters in this volume cover the histories, principles, and applications of individual techniques/technologies, and constitute stand-alone, yet interlinked lectures that strive to educate as well as to entertain. Besides providing an informative textbook for tertiary students in molecular biotechnology and related fields, this volume serves as an indispensable roadmap for novice scientists in their efforts to acquire innovative skills and establish solid track records in molecular biotechnology, and offers a contemporary reference for scholars, educators, and policymakers wishing to keep in touch with recent developments in molecular biotechnology.