Progress in Molecular Biology and Translational Science最新文献_第3页

Current approaches in CRISPR-Cas systems for hereditary diseases. 遗传疾病CRISPR-Cas系统的当前方法。

3区生物学

Progress in Molecular Biology and Translational Science Pub Date : 2025-01-01 Epub Date: 2024-08-22 DOI: 10.1016/bs.pmbts.2024.07.015

Swati Singh, Divakar Raj, Ashish Mathur, Neel Mani, Dhruv Kumar

{"title":"Current approaches in CRISPR-Cas systems for hereditary diseases.","authors":"Swati Singh, Divakar Raj, Ashish Mathur, Neel Mani, Dhruv Kumar","doi":"10.1016/bs.pmbts.2024.07.015","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.07.015","url":null,"abstract":"CRISPR-Cas technologies have drastically revolutionized genetic engineering and also dramatically changed the potential for treating inherited disorders. The potential to correct genetic mutations responsible for numerous hereditary disorders from single-gene disorders to complex polygenic diseases through precise DNA editing is feasible. The tactic now employed in CRISPR-Cas systems for treating inherited disorders is the usage of particular guide RNAs to target and edit disease-causing mutations in the patient's genome. Several methods such as CRISPR-Cas9, CRISPR-Cas12, and CRISPR-Cas13 are being thoroughly researched and optimized to increase effectiveness, accuracy, and safety in gene editing. Additionally, it is predicted that CRISPR-based therapies will be able to treat complex genetic illnesses such as cancer predisposition syndromes, neurological disorders, and cardiovascular conditions in addition to single-gene disorders. The available editing tools and creation of base editing technology facilitate the simultaneous correction of many mutations or accurate nucleotide changes leading to further advances in the development of multiplex editing tools and base editing technology fiction. When combined with other paradigms such as gene therapy using stem cell treatment, CRISPR-Cas promises improved efficacy. Patient treatment and lowering side effects significantly in individual genetic profiles will guide CRISPR-based treatments. These procedures will undoubtedly lead to therapies that are both efficient and curative of a wide range of genetic diseases, ushering in a new era of precision medicine. This chapter discusses about CRISPR Cas9 mechanism and its significance in the treatment of Hereditary disorders.","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"210 ","pages":"205-229"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014972","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}

引用次数: 0

Functional diversity of intrinsically disordered proteins and their structural heterogeneity: Protein structure-function continuum.

3区生物学

Progress in Molecular Biology and Translational Science Pub Date : 2025-01-01 Epub Date: 2025-02-05 DOI: 10.1016/bs.pmbts.2024.11.006

Vladimir N Uversky

{"title":"Functional diversity of intrinsically disordered proteins and their structural heterogeneity: Protein structure-function continuum.","authors":"Vladimir N Uversky","doi":"10.1016/bs.pmbts.2024.11.006","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.11.006","url":null,"abstract":"The fact that protein universe is enriched in intrinsic disorder is an accepted truism now. It is also recognized that the phenomenon of protein intrinsic disorder contains keys to answer numerous questions that do not have obvious solutions within the classic \"lock-and-key\"-based structure-function paradigm. In fact, reality is much more complex than the traditional \"one-gene - one-protein - one-function\" model, as many (if not most) proteins are multifunctional. This multifunctionality is commonly rooted in the presence of the intrinsically disordered or structurally flexible regions in a protein. Here, in addition to various events at the DNA (genetic variations), mRNA (alternative splicing, alternative promoter usage, alternative initiation of translation, and mRNA editing), and protein levels (post-translational modifications), intrinsic disorder and protein functionality are crucial for generation of proteoforms, which are functionally and structurally different protein forms produced from a single gene. Therefore, since a given protein exists as a dynamic conformational ensemble containing multiple proteoforms characterized by a broad spectrum of structural features and possessing various functional potentials, \"protein structure-function continuum\" model represents a more realistic way to correlate protein structure and function.","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"211 ","pages":"1-15"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415525","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}

引用次数: 0

Liquid-liquid phase separation of intrinsically disordered proteins: Effect of osmolytes and crowders.

3区生物学

Progress in Molecular Biology and Translational Science Pub Date : 2025-01-01 Epub Date: 2025-01-21 DOI: 10.1016/bs.pmbts.2024.11.005

G Priyanka, E Jawahar Raj, N Prakash Prabhu

{"title":"Liquid-liquid phase separation of intrinsically disordered proteins: Effect of osmolytes and crowders.","authors":"G Priyanka, E Jawahar Raj, N Prakash Prabhu","doi":"10.1016/bs.pmbts.2024.11.005","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.11.005","url":null,"abstract":"The formation of membraneless organelles is vital for the intracellular organization of macromolecules and in regulating many cellular processes. The membraneless organelles are formed by liquid-liquid phase separation (LLPS) mainly constituted of proteins and polynucleotides. The primary factor driving the liquid demixing into two phases is the multivalency of the proteins involved, a general characteristic of intrinsically disordered proteins (IDPs) or proteins with intrinsically disordered regions (IDRs). This chapter discusses the role of IDP/IDRs in biomolecular condensate formation and the physical characteristics of these states. Further, the LLPS formation of individual proteins induced by molecular crowding and its relevance to physiological conditions are presented. The studies on the effects of small molecular osmolytes and a hydrotrope, ATP on the phase separation temperature, protein concentration, and reentrant behavior are discussed. The advancements and limitations of the computational methods to predict the phase separation behavior of IDPs, and to analyze the interactions and dynamics of the proteins in condensates are presented. The roles of phase separation in cancer, neurological disorders, and cardiovascular diseases are highlighted.","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"211 ","pages":"249-269"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415710","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}

引用次数: 0

RNA therapeutics: Molecular mechanisms, and potential clinical translations. RNA 疗法：分子机制和潜在的临床应用。

3区生物学

Progress in Molecular Biology and Translational Science Pub Date : 2024-01-01 Epub Date: 2024-01-25 DOI: 10.1016/bs.pmbts.2023.12.012

Tiep Tien Nguyen, Yen Vi Nguyen Thi, Dinh-Toi Chu

{"title":"RNA therapeutics: Molecular mechanisms, and potential clinical translations.","authors":"Tiep Tien Nguyen, Yen Vi Nguyen Thi, Dinh-Toi Chu","doi":"10.1016/bs.pmbts.2023.12.012","DOIUrl":"10.1016/bs.pmbts.2023.12.012","url":null,"abstract":"RNA therapies involve the utilization of natural and artificial RNA molecules to control the expression and function of cellular genes and proteins. Initializing from 1990s, RNA therapies now show the rapid growth in the development and application of RNA therapeutics for treating various conditions, especially for undruggable diseases. The outstanding success of recent mRNA vaccines against COVID-19 infection again highlighted the important role of RNA therapies in future medicine. In this review, we will first briefly provide the crucial investigations on RNA therapy, from the first pieces of discovery on RNA molecules to clinical applications of RNA therapeutics. We will then classify the mechanisms of RNA therapeutics from various classes in the treatment of diseases. To emphasize the huge potential of RNA therapies, we also provide the key RNA products that have been on clinical trials or already FDA-approved. With comprehensive knowledge on RNA biology, and the advances in analysis, technology and computer-aid science, RNA therapies can bring a promise to be more expanding to the market in the future.","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"203 ","pages":"65-82"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742457","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}

引用次数: 0

Current progress in high-throughput screening for drug repurposing. 药物再利用高通量筛选的最新进展。

3区生物学

Progress in Molecular Biology and Translational Science Pub Date : 2024-01-01 Epub Date: 2024-04-16 DOI: 10.1016/bs.pmbts.2024.03.013

Khushal Khambhati, Deepak Siruka, Suresh Ramakrishna, Vijai Singh

引用次数: 0

An introduction to RNA therapeutics and their potentials. RNA 疗法及其潜力简介。

3区生物学

Progress in Molecular Biology and Translational Science Pub Date : 2024-01-01 Epub Date: 2024-01-25 DOI: 10.1016/bs.pmbts.2023.12.020

Nhat-Le Bui, Dinh-Toi Chu

{"title":"An introduction to RNA therapeutics and their potentials.","authors":"Nhat-Le Bui, Dinh-Toi Chu","doi":"10.1016/bs.pmbts.2023.12.020","DOIUrl":"10.1016/bs.pmbts.2023.12.020","url":null,"abstract":"RNA therapeutics is a biological term regarding the usage of RNA-based molecules for medical purposes. Thanks to the success of mRNA-vaccine production against COVID-19, RNA therapeutics has gained more and more attention and investigation from worldwide scientists. It is considered as one of the promising alternatives for conventional drugs. In this first chapter, we presented an overview of the history and perspectives of RNA therapeutics' development. This chapter also explained the underlying mechanisms of different RNA-based molecules, including antisense oligonucleotide, interfering RNA (iRNA), aptamer, and mRNA, from degrading mRNA to inactivating targeted protein. Although there are many advantages of RNA therapeutics, its challenges in designing RNA chemical structure and the delivery vehicle need to be discussed. We described advanced technologies in the development of drug delivery systems that are positively correlated to the efficacy of the drug. Our aim is to provide a general background of RNA therapeutics to the audience before introducing plenty of more detailed parts, including clinical applications in certain diseases in the following chapters of the \"RNA therapeutics\" book.","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"203 ","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742413","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}

引用次数: 0

RNA therapeutics for neurological disease. 治疗神经系统疾病的 RNA 疗法。

3区生物学

Progress in Molecular Biology and Translational Science Pub Date : 2024-01-01 Epub Date: 2024-01-24 DOI: 10.1016/bs.pmbts.2024.01.005

Lien Nguyen

{"title":"RNA therapeutics for neurological disease.","authors":"Lien Nguyen","doi":"10.1016/bs.pmbts.2024.01.005","DOIUrl":"10.1016/bs.pmbts.2024.01.005","url":null,"abstract":"Neurological disorders are the group of diseases that primarily affect the center nervous system, which could lead to a significant negative impact on the ability of learning new skills, speaking, breathing, walking, judging, making decision, and other essential living skills. In the last decade, neurological disorders have significantly increased their impact to our community and become the one of leading causes of disability and death. The World Health Organization has identified neurological disorders including Alzheimer's disease and other dementia as the health crisis for the modern life. Tremendous ongoing research efforts focus on understanding of disease genetics, molecular mechanisms and developing therapeutic interventions. Because of the urgent need of the effective therapeutics and the recent advances in the toolkits and understanding for developing more drug-like RNA molecules, there is a growing interest for developing RNA therapeutics for neurological disorders. This article will discuss genetics and mechanisms of neurological disorders and how RNA-based molecules have been used to develop therapeutics for this group of diseases, challenges of RNA therapeutics and future perspectives on this rising therapeutic intervention tool.","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"203 ","pages":"165-180"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742451","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}

引用次数: 0

RNA therapeutics for respiratory diseases. 呼吸系统疾病的 RNA 治疗。

3区生物学

Progress in Molecular Biology and Translational Science Pub Date : 2024-01-01 Epub Date: 2024-01-25 DOI: 10.1016/bs.pmbts.2023.12.021

Hue Vu Thi, Linh Thao Tran, Huy Quang Nguyen, Dinh-Toi Chu

引用次数: 0

Current approaches in identification of a novel drug targets for drug repurposing. 确定新药靶点以实现药物再利用的现有方法。

3区生物学

Progress in Molecular Biology and Translational Science Pub Date : 2024-01-01 Epub Date: 2024-04-04 DOI: 10.1016/bs.pmbts.2024.03.020

Khushal Khambhati, Vijai Singh

引用次数: 0

RNA therapeutics for metabolic disorders. 治疗代谢紊乱的 RNA 疗法。

3区生物学

Progress in Molecular Biology and Translational Science Pub Date : 2024-01-01 Epub Date: 2024-01-25 DOI: 10.1016/bs.pmbts.2023.12.014

Thuy-Duong Vu, Sheng-Che Lin, Chia-Ching Wu, Dinh-Toi Chu

{"title":"RNA therapeutics for metabolic disorders.","authors":"Thuy-Duong Vu, Sheng-Che Lin, Chia-Ching Wu, Dinh-Toi Chu","doi":"10.1016/bs.pmbts.2023.12.014","DOIUrl":"10.1016/bs.pmbts.2023.12.014","url":null,"abstract":"The prevalence of metabolic disorders is increasing exponentially and has recently reached epidemic levels. Over the decades, a large number of therapeutic options have been proposed to manage these diseases but still show several limitations. In this circumstance, RNA therapeutics have rapidly emerged as a new hope for patients with metabolic diseases. 57 years have elapsed from the discovery of mRNA, a large number of RNA-based drug candidates have been evaluated for their therapeutic effectiveness and clinical safety under clinical studies. To date, there are seven RNA drugs for treating metabolic disorders receiving official approval and entering the global market. Their targets include hereditary transthyretin-mediated amyloidosis (hATTR), familial chylomicronemia syndrome, acute hepatic porphyria, primary hyperoxaluria type 1 and hypercholesterolemia, which are all related to liver proteins. All of these seven RNA drugs are antisense oligonucleotides (ASO) and small interfering RNA (siRNA). These two types of treatment are both based on oligonucleotides complementary to target RNA through Watson-Crick base-pairing, but their mechanisms of action include different nucleases. Such treatments show greatest potential among all types of RNA therapeutics due to consecutive achievements in chemical modifications. Another method, mRNA therapeutics also promise a brighter future for patients with a handful of drug candidates currently under development.","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"203 ","pages":"181-196"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742450","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}

引用次数: 0