Progress in Molecular Biology and Translational Science最新文献

{"title":"Repurposing of biologics and biopharmaceuticals.","authors":"Juveriya Israr, Shabroz Alam, Vijai Singh, Ajay Kumar","doi":"10.1016/bs.pmbts.2024.03.028","DOIUrl":"10.1016/bs.pmbts.2024.03.028","url":null,"abstract":"<p><p>The field of drug repurposing is gaining attention as a way to introduce pharmaceutical agents with established safety profiles to new patient populations. This approach involves finding new applications for existing drugs through observations or deliberate efforts to understand their mechanisms of action. Recent advancements in bioinformatics and pharmacology, along with the availability of extensive data repositories and analytical techniques, have fueled the demand for novel methodologies in pharmaceutical research and development. To facilitate systematic drug repurposing, various computational methodologies have emerged, combining experimental techniques and in silico approaches. These methods have revolutionized the field of drug discovery by enabling the efficient repurposing of screens. However, establishing an ideal drug repurposing pipeline requires the integration of molecular data accessibility, analytical proficiency, experimental design expertise, and a comprehensive understanding of clinical development processes. This chapter explores the key methodologies used in systematic drug repurposing and discusses the stakeholders involved in this field. It emphasizes the importance of strategic alliances to enhance the success of repurposing existing compounds for new indications. Additionally, the chapter highlights the current benefits, considerations, and challenges faced in the repurposing process, which is pursued by both biotechnology and pharmaceutical companies. Overall, drug repurposing holds great promise in expanding the use of existing drugs and bringing them to new patient populations. With the advancements in computational methodologies and the collaboration of various stakeholders, this approach has the potential to accelerate drug development and improve patient outcomes.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"205 ","pages":"277-302"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel strategies for drug repurposing.","authors":"Mutsa Monica Takundwa, Deepak B Thimiri Govinda Raj","doi":"10.1016/bs.pmbts.2024.03.021","DOIUrl":"10.1016/bs.pmbts.2024.03.021","url":null,"abstract":"<p><p>Synthetic biology, precision medicine, and nanobiotechnology are the three main emerging areas that drive translational innovation toward commercialization. There are several strategies used in precision medicine and drug repurposing is one of the key approaches as it addresses the challenges in drug discovery (high cost and time). Here, we provide a perspective on various new approaches to drug repurposing for cancer precision medicine. We report here our optimized wound healing methodology that can be used to validate drug sensitivity and drug repurposing. Using HeLa as our benchmark, we demonstrated that the assay can be applied to identify drugs that limit cell proliferation. From a future perspective, this assay can be expanded to ex vivo culturing of solid tumors in 2D culture and leukemia in 3D culture.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"205 ","pages":"9-21"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative target mining stratagems to navigate drug repurposing endeavours.","authors":"Kamatchi Sundara Saravanan, Kshreeraja S Satish, Ganesan Rajalekshmi Saraswathy, Ushnaa Kuri, Soujanya J Vastrad, Ritesh Giri, Prizvan Lawrence Dsouza, Adusumilli Pramod Kumar, Gouri Nair","doi":"10.1016/bs.pmbts.2024.03.025","DOIUrl":"10.1016/bs.pmbts.2024.03.025","url":null,"abstract":"<p><p>The conventional theory linking a single gene with a particular disease and a specific drug contributes to the dwindling success rates of traditional drug discovery. This requires a substantial shift focussing on contemporary drug design or drug repurposing, which entails linking multiple genes to diverse physiological or pathological pathways and drugs. Lately, drug repurposing, the art of discovering new/unlabelled indications for existing drugs or candidates in clinical trials, is gaining attention owing to its success rates. The rate-limiting phase of this strategy lies in target identification, which is generally driven through disease-centric and/or drug-centric approaches. The disease-centric approach is based on exploration of crucial biomolecules such as genes or proteins underlying pathological cascades of the disease of interest. Investigating these pathological interplays aids in the identification of potential drug targets that can be leveraged for novel therapeutic interventions. The drug-centric approach involves various strategies such as exploring the mechanism of adverse drug reactions that can unearth potential targets, as these untoward reactions might be considered desirable therapeutic actions in other disease conditions. Currently, artificial intelligence is an emerging robust tool that can be used to translate the aforementioned intricate biological networks to render interpretable data for extracting precise molecular targets. Integration of multiple approaches, big data analytics, and clinical corroboration are essential for successful target mining. This chapter highlights the contemporary strategies steering target identification and diverse frameworks for drug repurposing. These strategies are illustrated through case studies curated from recent drug repurposing research inclined towards neurodegenerative diseases, cancer, infections, immunological, and cardiovascular disorders.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"205 ","pages":"303-355"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of data science and bioinformatics in RNA therapeutics.","authors":"Hue Vu Thi, Thanh-Nhat Hoang, Nguyen Quoc Khanh Le, Dinh-Toi Chu","doi":"10.1016/bs.pmbts.2023.12.019","DOIUrl":"10.1016/bs.pmbts.2023.12.019","url":null,"abstract":"<p><p>Nowadays, information technology (IT) has been holding a significant role in daily life worldwide. The trajectory of data science and bioinformatics promises pioneering personalized therapies, reshaping medical landscapes and patient care. For RNA therapy to reach more patients, a comprehensive understanding of the application of data science and bioinformatics to this therapy is essential. Thus, this chapter has summarized the application of data science and bioinformatics in RNA therapeutics. Data science applications in RNA therapy, such as data integration and analytics, machine learning, and drug development, have been discussed. In addition, aspects of bioinformatics such as RNA design and evaluation, drug delivery system simulation, and databases for personalized medicine have also been covered in this chapter. These insights have shed light on existing evidence and opened potential future directions. From there, scientists can elevate RNA-based therapeutics into an era of tailored treatments and revolutionary healthcare.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"203 ","pages":"83-97"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational tools supporting known miRNA identification.","authors":"Van-Quy Do, Chuc Hoang-Thi, Thanh-Truong Pham, Nhat-Le Bui, Dinh-Thai Kim, Dinh-Toi Chu","doi":"10.1016/bs.pmbts.2023.12.018","DOIUrl":"10.1016/bs.pmbts.2023.12.018","url":null,"abstract":"<p><p>The study of small RNAs is a field that is expanding quickly. Other functional short RNA molecules other than microRNAs, and gene expression regulators, have been found in animals and plants. MicroRNAs play a significant role in host-microbe interactions, and parasite microRNAs may affect the host's innate immunity. Furthermore, short RNAs are intriguing non-invasive biomarker possibilities because they can be found in physiological fluids. These trends suggest that for many researchers, quick and simple techniques for expression profiling and subsequent downstream analysis of miRNA-seq data are crucial. We selected sRNAtoolbox to make integrated sRNA research easier. Each tool can be used separately or to explore and analyze sRNAbench results in further depth. A special focus was placed on the tools' usability. We review available miRNA research tools to have an overview of the evaluation of the tools. Mainly we evaluate the tool sRNAtoolbox.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"203 ","pages":"225-242"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA therapeutics history and future perspectives.","authors":"Hong-Quan Duong, Minh-Cong Hoang, Thi-Hue Nguyen, Van-Lang Ngo, Van-Thu Le","doi":"10.1016/bs.pmbts.2024.01.004","DOIUrl":"10.1016/bs.pmbts.2024.01.004","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"203 ","pages":"99-114"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The development and technologies of RNA therapeutics.","authors":"Huong Lan Vuong, Chu Thanh Lan, Hien Thi Thu Le","doi":"10.1016/bs.pmbts.2023.12.017","DOIUrl":"10.1016/bs.pmbts.2023.12.017","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"203 ","pages":"13-39"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of artificial intelligence and machine learning in drug repurposing.","authors":"Sudhir K Ghandikota, Anil G Jegga","doi":"10.1016/bs.pmbts.2024.03.030","DOIUrl":"10.1016/bs.pmbts.2024.03.030","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"205 ","pages":"171-211"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"System biology approaches for drug repurposing.","authors":"Juveriya Israr, Shabroz Alam, Ajay Kumar","doi":"10.1016/bs.pmbts.2024.03.027","DOIUrl":"10.1016/bs.pmbts.2024.03.027","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"205 ","pages":"221-245"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergizing drug repurposing and target identification for neurodegenerative diseases.","authors":"Mehar Sahu, Shrutikirti Vashishth, Neha Kukreti, Ashima Gulia, Ashish Russell, Rashmi K Ambasta, Pravir Kumar","doi":"10.1016/bs.pmbts.2024.03.023","DOIUrl":"10.1016/bs.pmbts.2024.03.023","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"205 ","pages":"111-169"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}