Progress in molecular biology and translational science最新文献

The CRISPR-Cas9 method has revolutionized the gene editing. Epigenetic changes, including DNA methylation, RNA modification, and changes in histone proteins, have been intensively studied and found to play a key role in the pathogenesis of human diseases. CRISPR-While the utility of DNA and chromatin modifications, known as epigenetics, is well understood, the functional significance of various alterations of RNA nucleotides has recently gained attention. Recent advancements in improving CRISPR-based epigenetic modifications has resulted in the availability of a powerful source that can selectively modify DNA, allowing for the maintenance of epigenetic memory over several cell divisions. Accurate identification of DNA methylation at specific locations is crucial for the prompt detection of cancer and other diseases, as DNA methylation is strongly correlated to the onset as well as the advancement of such conditions. Genetic or epigenetic perturbations can disrupt the regulation of imprinted genes, resulting in the development of diseases. When histone code editors and DNA de-/ methyltransferases are coupled with catalytically inactive Cas9 (dCas9), and CRISPRa and CRISPRi, they demonstrate excellent efficacy in editing the epigenome of eukaryotic cells. Advancing and optimizing the extracellular delivery platform can, hence, further facilitate the manipulation of CRISPR-Cas9 gene editing technique in upcoming clinical studies. The current chapter focuses on how the CRISP/ Cas9 system provides an avenue for the epigenetic modifications and its employability for human benefit.

Fungi contain a wide range of bioactive secondary metabolites (SMs) that have numerous applications in various fields, including agriculture, medicine, human health, and more. It is common for genes responsible for the production of secondary metabolites (SMs) to form biosynthetic gene clusters (BGCs). The identification and analysis of numerous unexplored gene clusters (BGCs) and their corresponding substances (SMs) has been significantly facilitated by the recent advancements in genomic and genetic technologies. Nevertheless, the exploration of secondary metabolites with commercial value is impeded by a variety of challenges. The emergence of modern CRISPR/Cas technologies has brought about a paradigm shift in fungal genetic engineering, significantly streamlining the process of discovering new bioactive compounds. This study begins with an examination of fungal biosynthetic gene clusters (BGCs) and their interconnections with the secondary metabolites (SMs) they generate. Following that, a brief summary of the conventional methods employed in fungal genetic engineering is provided. This study explores various sophisticated CRISPR/Cas-based methodologies and their utilization in examining the synthesis of secondary metabolites (SMs) in fungi. The chapter provides an in-depth analysis of the limitations and obstacles encountered in CRISPR/Cas-based systems when applied to fungal genetic engineering. It also proposes promising avenues for future research to optimize the efficiency of these systems.

Cancer immunotherapy is a revolutionised strategy that strikingly improves cancer treatment in recent years. However, like other therapeutic modalities, immunotherapy faces several challenges and limitations. Many methods have been developed to overcome those limitations; thus, nanomedicine is one of the emerging fields with a highly promising application. Magnetite nanoparticles (MNPs) have long been used for medical applications, for example, as a contrast medium, and are being investigated as a tool for boosting and synergizing the effects of immunotherapy. With known physicochemical properties and the interaction with the surroundings in biological systems, MNPs are used to improve the efficacy of immunotherapy in both cell-based and antibody-based treatment. This chapter reviews and discusses state-of-the-art MNPs as a tool to advance cancer immunotherapy as well as its limitations that need further investigation for a better therapeutic outcome in preclinical and clinical settings.

RNA therapy has recently emerged as a therapy targeting specific genes or proteins. With its outstanding advantages, this therapy has opened promising doors for treating and preventing diseases. The great application potential has driven the need for a comprehensive understanding of these therapies, particularly on biosafety and regulatory issues. This chapter began by discussing the risks to RNA therapy, such as off-target effects, immunogenicity and immune responses, and long-term effects. Since then, this therapy's intricate landscape of biosafety issues has been elucidated. Common biosecurity measures applied around the world have also been reviewed. In addition, this chapter emphasized the importance of regulations and laws in applying RNA therapy to prevent and treat human and animal diseases. At the same time, the current legal regulations in the world for RNA therapies have also been thoroughly discussed. To sum up, this chapter has provided a comprehensive perspective on biosafety and regulatory issues for developing RNA therapies. Understanding the biosafety and regulatory issues in RNA therapy can help researchers use this promising new technology safely and effectively in the future.

The pathogenesis of COVID-19 involves a complex interplay between host factors and the SARS-CoV-2 virus, leading to a multitude of clinical manifestations beyond the respiratory system. This chapter provides an overview of the risk factors, genetic predisposition, and multisystem manifestations of COVID-19, shedding light on the underlying mechanisms that contribute to extrapulmonary manifestations. The chapter discusses the direct invasion of SARS-CoV-2 into various organs as well as the indirect mechanisms such as dysregulation of the renin-angiotensin-aldosterone system (RAAS), immune response dysfunctions within the innate and adaptive immune systems, endothelial damage, and immunothrombosis. Furthermore, the multisystem manifestations of COVID-19 across different organ systems, including the cardiovascular, renal, gastrointestinal, hepatobiliary, nervous, endocrine and metabolic, ophthalmic, ear-nose-throat, reproductive, hematopoietic, and immune systems are discussed in detail. Each system exhibits unique manifestations that contribute to the complexity of the disease.

The scientific community is very interested in protein aggregation because of its involvement in several neurodegenerative diseases and its significance in industry. Remarkably, fibrillar aggregates are utilized naturally for constructing structural scaffolds or creating biological switches and may be intentionally designed to construct versatile nanomaterials. Consequently, there is a significant need to rationalize and predict protein aggregation. Researchers have developed various computational methodologies and algorithms to predict protein aggregation and understand its underlying mechanics. This chapter aims to summarize the significant advancements in computational methods, accessible resources, and prospective developments in the field of in silico research. We assess the existing computational tools for predicting protein aggregation propensities, detecting areas that are prone to sequential and structural aggregation, analyzing the effects of mutations on protein aggregation, or identifying prion-like domains.

Repurposing pharmaceuticals is a technique used to find new, alternate clinical applications for approved drug molecules. It may include altering the drug formulation, route of administration, dose or the dosage regimen. The process of repurposing medicines starts with screening libraries of previously approved drugs for the targeted disease condition. If after an the initial in silico, in vitro or in vivo experimentation, the molecule has been found to be active against a particular target, the molecule is considered as a good candidate for clinical trials. As the safety profile of such molecules is available from the previous data, significant time and resources are saved. These advantages of drug repurposing approach make it especially helpful for finding treatments for rapidly evolving conditions including bacterial infections. An ever-increasing incidence of antimicrobial resistance, owing to the mutations in bacterial genome, leads to therapeutic failure of many approved antibiotics. Repurposing the approved drug molecules for use as antibiotics can provide an effective means for the combating life-threatening bacterial diseases. A number of drugs have been considered for drug repurposing against bacterial infections. These include, but are not limited to, Auranofin, Closantel, and Toremifene that have been repurposed for various infections. In addition, the reallocation of route of administration, redefining dosage regimen and reformulation of dosage forms have also been carried out for repurposing purpose. The current chapter addresses the drug discovery and development process with relevance to repurposing against bacterial infections.

The rise of multidrug-resistant bacteria is a well-recognized threat to world health, necessitating the implementation of effective treatments. This issue has been identified as a top priority on the global agenda by the World Health Organization. Certain strains, such as Candida glabrata, Candida krusei, Candida lusitaniae, Candida auris, select cryptococcal species, and opportunistic Aspergillus or Fusarium species, have significant intrinsic resistance to numerous antifungal medicines. This inherent resistance and subsequent suboptimal clinical outcomes underscore the critical imperative for enhanced therapeutic alternatives and management protocols. The challenge of effectively treating fungal infections, compounded by the protracted timelines involved in developing novel drugs, underscores the pressing need to explore alternative therapeutic avenues. Among these, drug repurposing emerges as a particularly promising and expeditious solution, providing cost-effective solutions and safety benefits. In the fight against life-threatening resistant fungal infections, the idea of repurposing existing medications has encouraged research into both established and new compounds as a last-resort therapy. This chapter seeks to provide a comprehensive overview of contemporary antifungal drugs, as well as their key resistance mechanisms. Additionally, it seeks to provide insight into the antimicrobial properties of non-traditional drugs, thereby offering a holistic perspective on the evolving landscape of antifungal therapeutics.

Protein aggregates and amyloid fibrils have special qualities and are used in a variety of biotechnological applications. They are extensively employed in bioremediation, biomaterials, and biocatalysis. Because of their capacity to encapsulate and release pharmaceuticals and their sensitivity to certain molecules, respectively, they are also used in drug delivery and biosensor applications. They have also demonstrated potential in the domains of food and bioremediation. Additionally, amyloid peptides have drawn interest in biological applications, especially in the investigation of illnesses like Parkinson's and Alzheimer's. The unique characteristics of amyloid fibrils, namely their mechanical strength and β-sheet structure, make them adaptable to a wide range of biotechnological uses. Even with their promise, one important factor to keep in mind before widely using modified amyloid materials is their potential toxicity. Thus, current research aims to overcome safety concerns while maximizing their potential.