Progress in Molecular Biology and Translational Science最新文献

Ribonucleic acid (RNA) therapeutics have significantly used RNA-based drugs to the prevention and treatment of diseases as effective messenger RNA-based vaccines in response to the COVID-19 pandemic. The RNA therapeutics with five classes including antisense oligonucleotide, small interfering RNA, microRNA, APTAMER and messenger RNAs are being quickly developed to treat various human diseases as neurological disease, cardiovascular disease, genetic and rare disease, cancer disease, coronavirus disease… which cannot be treated by other conventional drugs as small molecule-based drugs and antibodies. Therefore, the discovery of these RNA therapeutics created a new avenue for treatment of various human diseases. This chapter demonstrates the history of important discoveries in RNA biology and their impact on key developments in RNA therapeutics as well as the advantages of RNA therapeutics; RNA therapeutics describes the action mechanisms and examples of RNA-based drugs approved for treatment of various disease; and RNA therapeutics discusses delivery methods for RNA therapeutics to target organs and cells. In conclusion, this chapter is designed to offer an updated important development and advance of RNA therapeutics for the prevention and treatment of various human diseases.

Since it was discovered for over 20 years ago, the potentiality of siRNAs in gene silencing in vitro and in vivo models has been recognized. Several studies in the new generation, molecular mechanisms, target attachment, and purification of RNA have supported the development of RNA therapeutics for a variety of applications. RNA therapeutics are growing rapidly with various platforms contributing to the standard of personalized medicine and rare disease treatment. Therefore, understanding the development and technologies of RNA therapeutics becomes a crucial point for new drug generation. Here, the primary purpose of this review is to provide a general view of six therapeutic categories that make up RNA-based therapeutic approaches, including RNA-target therapeutics, protein-targeted therapeutics, cellular reprogramming and tissues engineering, RNA-based protein replacement therapeutics, RNA-based genome editing, and RNA-based immunotherapies based on non-coding RNAs and coding RNA. Furthermore, we present an overview of the RNA strategies regarding viral approaches and nonviral approaches in designing a new generation of RNA technologies. The advantages and challenges of using RNA therapeutics are also discussed along with various approaches for RNA delivery. Therefore, this review is designed to provide updated reference evidence of RNA therapeutics in the battle against rare or difficult-to-treat diseases for researchers in this field.

The purpose of drug repurposing is to leverage previously approved drugs for a particular disease indication and apply them to another disease. It can be seen as a faster and more cost-effective approach to drug discovery and a powerful tool for achieving precision medicine. In addition, drug repurposing can be used to identify therapeutic candidates for rare diseases and phenotypic conditions with limited information on disease biology. Machine learning and artificial intelligence (AI) methodologies have enabled the construction of effective, data-driven repurposing pipelines by integrating and analyzing large-scale biomedical data. Recent technological advances, especially in heterogeneous network mining and natural language processing, have opened up exciting new opportunities and analytical strategies for drug repurposing. In this review, we first introduce the challenges in repurposing approaches and highlight some success stories, including those during the COVID-19 pandemic. Next, we review some existing computational frameworks in the literature, organized on the basis of the type of biomedical input data analyzed and the computational algorithms involved. In conclusion, we outline some exciting new directions that drug repurposing research may take, as pioneered by the generative AI revolution.

Drug repurposing, or drug repositioning, refers to the identification of alternative therapeutic applications for established medications that go beyond their initial indications. This strategy has becoming increasingly popular since it has the potential to significantly reduce the overall costs of drug development by around $300 million. System biology methodologies have been employed to facilitate medication repurposing, encompassing computational techniques such as signature matching and network-based strategies. These techniques utilize pre-existing drug-related data types and databases to find prospective repurposed medications that have minimal or acceptable harmful effects on patients. The primary benefit of medication repurposing in comparison to drug development lies in the fact that approved pharmaceuticals have already undergone multiple phases of clinical studies, thereby possessing well-established safety and pharmacokinetic properties. Utilizing system biology methodologies in medication repurposing offers the capacity to expedite the discovery of viable candidates for drug repurposing and offer novel perspectives for structure-based drug design.

Despite dedicated research efforts, the absence of disease-curing remedies for neurodegenerative diseases (NDDs) continues to jeopardize human society and stands as a challenge. Drug repurposing is an attempt to find new functionality of existing drugs and take it as an opportunity to discourse the clinically unmet need to treat neurodegeneration. However, despite applying this approach to rediscover a drug, it can also be used to identify the target on which a drug could work. The primary objective of target identification is to unravel all the possibilities of detecting a new drug or repurposing an existing drug. Lately, scientists and researchers have been focusing on specific genes, a particular site in DNA, a protein, or a molecule that might be involved in the pathogenesis of the disease. However, the new era discusses directing the signaling mechanism involved in the disease progression, where receptors, ion channels, enzymes, and other carrier molecules play a huge role. This review aims to highlight how target identification can expedite the whole process of drug repurposing. Here, we first spot various target-identification methods and drug-repositioning studies, including drug-target and structure-based identification studies. Moreover, we emphasize various drug repurposing approaches in NDDs, namely, experimental-based, mechanism-based, and in silico approaches. Later, we draw attention to validation techniques and stress on drugs that are currently undergoing clinical trials in NDDs. Lastly, we underscore the future perspective of synergizing drug repurposing and target identification in NDDs and present an unresolved question to address the issue.

Identification and implementation of novel drug are not only time consuming and expensive but also it poses huge challenge to reach into the market. Currently, thousands of USFDA approved drugs licence are being expired that can be repurposed for treating other diseases. Drug repurposing is an alternative solution to reduce time, cost and steps for development of drugs and their applications for treating disease. The current chapter emphases to brief the steps involved in drug discovery and drug repurposing. The chapter also includes repurposed drugs for treating bacterial, fungal and viral diseases. Unlocking the potential of already existed drug and repurposing them for other diseases that could accelerate drug discovery and aid in managing outbreaks.

Blood disorders are defined as diseases related to the structure, function, and formation of blood cells. These diseases lead to increased years of life loss, reduced quality of life, and increased financial burden for social security systems around the world. Common blood disorder treatments such as using chemical drugs, organ transplants, or stem cell therapy have not yet approached the best goals, and treatment costs are also very high. RNA with a research history dating back several decades has emerged as a potential method to treat hematological diseases. A number of clinical trials have been conducted to pave the way for the use of RNA molecules to cure blood disorders. This novel approach takes advantage of regulatory mechanisms and the versatility of RNA-based oligonucleotides to target genes and cellular pathways involved in the pathogenesis of specific diseases. Despite positive results, currently, there is no RNA drug to treat blood-related diseases approved or marketed. Before the clinical adoption of RNA-based therapies, challenges such as safe delivery of RNA molecules to the target site and off-target effects of injected RNA in the body need to be addressed. In brief, RNA-based therapies open novel avenues for the treatment of hematological diseases, and clinical trials for approval and practical use of RNA-targeted are crucial.

Ribonucleic acid (RNA) therapy has been extensively researched for several decades and has garnered significant attention in recent years owing to its potential in treating a broad spectrum of diseases. It falls under the domain of gene therapy, leveraging RNA molecules as a therapeutic approach in medicine. RNA can be targeted using small-molecule drugs, or RNA molecules themselves can serve as drugs by interacting with proteins or other RNA molecules. While several RNA drugs have been granted clinical approval, numerous RNA-based therapeutics are presently undergoing clinical investigation or testing for various conditions, including genetic disorders, viral infections, and diverse forms of cancer. These therapies offer several advantages, such as high specificity, enabling precise targeting of disease-related genes or proteins, cost-effectiveness, and a relatively straightforward manufacturing process. Nevertheless, successful translation of RNA therapies into widespread clinical use necessitates addressing challenges related to delivery, stability, and potential off-target effects. This chapter provides a comprehensive overview of the general concepts of various classes of RNA-based therapeutics, the mechanistic basis of their function, as well as recent applications of RNA therapeutic in clinics.

Medications that are currently on the market and have proven therapeutic usage can have new therapeutic indications discovered through a process called drug repurposing, which is also called drug repositioning. This approach presents a viable method for drug developers and pharmaceutical companies to discern novel targets for FDA-approved medications. Drug repurposing presents several advantages, including reduced time consumption, lower costs, and diminished risk of failure. Sildenafil, commonly known as Viagra, serves as a notable illustration of a repurposed pharmaceutical agent, initially developed and introduced to the market as an antianginal medication. However, in the current context, its application has been redirected towards serving as a pharmaceutical intervention for the treatment of erectile dysfunction. Comparably, a multitude of pharmaceutical agents exist that have demonstrated efficacy in repurposing for therapeutic management of various clinical conditions. Focusing on the historical use of repurposed pharmaceuticals and their present state of application in disease therapies, this chapter seeks to offer a thorough review of drug repurposing methodologies. Furthermore, the rules and regulations that control the repurposing of drugs will be covered in detail in this chapter.

The lab-on-chip technique broadly comprises of microfluidics and aims to progress multidimensionally by changing the outlook of medicine and pharmaceuticals as it finds it roots in miniaturization. Moreover, microfluidics facilitates precise physiological simulation and possesses biological system-mimicking capabilities for drug development and repurposing. Thus, organs on chip could pave a revolutionary pathway in the field of drug development and repurposing by reducing animal testing and improving drug repurposing.