Progress in Molecular Biology and Translational Science最新文献

{"title":"An overview to drug repurposing.","authors":"Khushal Khambhati, Abdulrahman H Alessa, Vijai Singh","doi":"10.1016/bs.pmbts.2024.03.026","DOIUrl":"10.1016/bs.pmbts.2024.03.026","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"205 ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094521","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 for the treatment of blood disorders.","authors":"Anh Dao Ngo, Hoang Lam Nguyen, Safak Caglayan, Dinh-Toi Chu","doi":"10.1016/bs.pmbts.2023.11.005","DOIUrl":"10.1016/bs.pmbts.2023.11.005","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"203 ","pages":"273-286"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742453","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":"Recent applications of RNA therapeutic in clinics.","authors":"Huyen Trang Ha Thi, Van Thai Than","doi":"10.1016/bs.pmbts.2023.12.015","DOIUrl":"10.1016/bs.pmbts.2023.12.015","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"203 ","pages":"115-150"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742416","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":"Approaches of pre-clinical and clinical trials of repurposed drug.","authors":"Juveriya Israr, Shabroz Alam, Ajay Kumar","doi":"10.1016/bs.pmbts.2024.03.024","DOIUrl":"10.1016/bs.pmbts.2024.03.024","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"205 ","pages":"259-275"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094546","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":"Lab on chip for testing of repurposed drugs.","authors":"Malvika Shukla, Saloni Malik, Alok Pandya","doi":"10.1016/bs.pmbts.2024.03.022","DOIUrl":"10.1016/bs.pmbts.2024.03.022","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"205 ","pages":"71-90"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094554","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":"Genome editing for phage design and uses for therapeutic applications.","authors":"Karthik Loganathan,&nbsp;Baskaran Viswanathan","doi":"10.1016/bs.pmbts.2023.03.012","DOIUrl":"10.1016/bs.pmbts.2023.03.012","url":null,"abstract":"<p><p>The over usage of antibiotics leads to antibiotic abuse which in turn eventually raises resistance mechanisms among wide range of pathogens. Due to lack of experimental data of efficacy of phages as potential antimicrobial and therapeutic agent and also more specific and cumbersome isolation process against specific pathogens makes it not so feasible technology to be looked as an alternative therapy. But, recent developments in genome editing techniques enables programmed nuclease enzymes that has effectively improvised our methodology to make accurate changes in the genomes of prokaryote as well as eukaryote cells. It is already strengthening our ability to improvise genetic engineering to disease identification by facilitating the creation of more precise models to identify the root cause. The present chapter discusses on improvisation of phage therapy using recent genome editing tools and also shares data on the methods of usage of phages and their derivatives like proteins and enzymes such as lysins and depolymerases, as a potential therapeutic or prophylaxis agent. Methods involved in recombinant based techniques were also discussed in this chapter. Combination of traditional approach with modern tools has led to a potential development of phage-based therapeutics in near future.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"201 ","pages":"203-224"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41157466","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":"Phages as delivery vehicles and phage display.","authors":"Salsabil Makky,&nbsp;Fatma Abdelrahman,&nbsp;Maheswaran Easwaran,&nbsp;Anan Safwat,&nbsp;Ayman El-Shibiny","doi":"10.1016/bs.pmbts.2023.03.013","DOIUrl":"10.1016/bs.pmbts.2023.03.013","url":null,"abstract":"<p><p>Bacteriophages (Phages in short) were introduced as the natural enemy of bacteria that may act as alternatives to antibiotics to overcome the challenge of antibiotic resistance. However, in the recent history of science, phages have been employed in different molecular tools and used in numerous therapeutic and diagnostic approaches. Furthermore, thanks to the phage`s highly specific host range limited to prokaryotes, phage particles can be used as safe delivery vehicles and display systems. In this chapter, different phage display systems are introduced, in addition to various applications of phage display as a molecular and therapeutic tool in developing vaccines, antibacterial, and anti-cancer treatments.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"201 ","pages":"119-132"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41138346","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":"Phages for the treatment of Mycobacterium species.","authors":"Christoffel Johannes Opperman,&nbsp;Justyna Wojno,&nbsp;Wynand Goosen,&nbsp;Rob Warren","doi":"10.1016/bs.pmbts.2023.03.016","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2023.03.016","url":null,"abstract":"<p><p>Highly drug-resistant strains are not uncommon among the Mycobacterium genus, with patients requiring lengthy antibiotic treatment regimens with multiple drugs and harmful side effects. This alarming increase in antibiotic resistance globally has renewed the interest in mycobacteriophage therapy for both Mycobacterium tuberculosis complex and non-tuberculosis mycobacteria. With the increasing number of genetically well-characterized mycobacteriophages and robust engineering tools to convert temperate phages to obligate lytic phages, the phage cache against extensive drug-resistant mycobacteria is constantly expanding. Synergistic effects between phages and TB drugs are also a promising avenue to research, with mycobacteriophages having several additional advantages compared to traditional antibiotics due to their different modes of action. These advantages include less side effects, a narrow host spectrum, biofilm penetration, self-replication at the site of infection and the potential to be manufactured on a large scale. In addition, mycobacteriophage enzymes, not yet in clinical use, warrant further studies with their additional benefits for rupturing host bacteria thereby limiting resistance development as well as showing promise in vitro to act synergistically with TB drugs. Before mycobacteriophage therapy can be envisioned as part of routine care, several obstacles must be overcome to translate in vitro work into clinical practice. Strategies to target intracellular bacteria and selecting phage cocktails to limit cross-resistance remain important avenues to explore. However, insight into pathophysiological host-phage interactions on a molecular level and innovative solutions to transcend mycobacteriophage therapy impediments, offer sufficient encouragement to explore phage therapy. Recently, the first successful clinical studies were performed using a mycobacteriophage-constructed cocktail to treat non-tuberculosis mycobacteria, providing substantial insight into lessons learned and potential pitfalls to avoid in order to ensure favorable outcomes. However, due to mycobacterium strain variation, mycobacteriophage therapy remains personalized, only being utilized in compassionate care cases until there is further regulatory approval. Therefore, identifying the determinants that influence clinical outcomes that can expand the repertoire of mycobacteriophages for therapeutic benefit, remains key for their future application.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"201 ","pages":"41-92"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41138347","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":"Phage display and human disease detection.","authors":"Sonu Kumari,&nbsp;Krati Singh,&nbsp;Neha Singh,&nbsp;Suphiya Khan,&nbsp;Ajay Kumar","doi":"10.1016/bs.pmbts.2023.03.022","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2023.03.022","url":null,"abstract":"<p><p>Phage display is a significant and active molecular method and has continued crucial for investigative sector meanwhile its unearthing in 1985. This practice has numerous benefits: the association among physiology and genome, the massive variety of variant proteins showed in sole collection and the elasticity of collection that can be achieved. It suggests a diversity of stages for manipulating antigen attachment; yet, variety and steadiness of exhibited library are an alarm. Additional improvements, like accumulation of non-canonical amino acids, resulting in extension of ligands that can be recognized through collection, will support in expansion of the probable uses and possibilities of technology. Epidemic of COVID-19 had taken countless lives, and while indicative prescriptions were provided to diseased individuals, still no prevention was observed for the contamination. Phage demonstration has presented an in-depth understanding into protein connections included in pathogenesis. Phage display knowledge is developing as an influential, inexpensive, quick, and effectual method to grow novel mediators for the molecular imaging and analysis of cancer.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"201 ","pages":"151-172"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41144627","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":"Synthetic phage and its application in phage therapy.","authors":"Ajay Kumar,&nbsp;Anuj Yadav","doi":"10.1016/bs.pmbts.2023.03.009","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2023.03.009","url":null,"abstract":"<p><p>Synthetic phage analysis has been implemented in progressive various areas of biology, such as genetics, molecular biology, and synthetic biology. Many phage-derived technologies have been altered for developing gene circuits to program biological systems. Due to their extremely potent potency, phages also provide greater medical availability against bacterial agents and bacterial diagnostic agents. Its host specificity and our growing ability to manipulate, them further expand its possibility. New Phages also genetically redesign programmable biomaterials with highly tunable properties. Moreover, new phages are central to powerful directed evolution platforms. It is used to enhance existing biological, functions to create new phages. In other sites, the mining of antibiotics, and the emergence and dissemination of more than one type of drug-resistant microbe, a human health concerns. The major point in controlling and treating microbial infections. At present, genetic modifications and biochemical treatments are used to modify phages. Among these, genetic engineering involves the identification of defective proteins, modification of host bodies, recognized receptors, and disruption of bacterial phage resistance signaling gateways.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"200 ","pages":"61-89"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41162104","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}