Molecular Therapy. Nucleic Acids最新文献_第2页

The potential and challenges of circular RNA in the development of vaccines and drugs for emerging infectious diseases. 环状RNA在新发传染病疫苗和药物开发中的潜力和挑战。

IF 6.1 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2025-08-14 eCollection Date: 2025-09-09 DOI: 10.1016/j.omtn.2025.102687

Keda Chen, Yutong Xu, Jiaxuan Li, Siyi Gu, Zhiyi Wang, Jianhua Li, Yanjun Zhang

{"title":"The potential and challenges of circular RNA in the development of vaccines and drugs for emerging infectious diseases.","authors":"Keda Chen, Yutong Xu, Jiaxuan Li, Siyi Gu, Zhiyi Wang, Jianhua Li, Yanjun Zhang","doi":"10.1016/j.omtn.2025.102687","DOIUrl":"10.1016/j.omtn.2025.102687","url":null,"abstract":"Circular RNAs (circRNAs) are a class of RNA molecules with a covalent closed-loop structure that play important roles in the regulation of biological processes and disease genesis. In recent years, circRNAs have become a research hotspot due to their unique stability and biological functions. Compared with linear RNAs, synthetic circRNAs have higher stability and show great potential in therapeutic applications. Although circRNA technology is still at an early stage of development, breakthroughs in mRNA technology provide an important reference for its application. This review systematically explores the promising applications of circRNAs in vaccine development and drug research, evaluates their feasibility as vaccine components and drug carriers, and experimentally validates their efficacy in disease models. At the same time, this paper analyzes the advantages and challenges of circRNA application in depth and looks forward to the future research direction, which provides new ideas for the prevention and treatment of new outbreaks of infectious diseases.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"36 3","pages":"102687"},"PeriodicalIF":6.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ASOs reduce SARS-CoV-2 viral titers in Syrian golden hamsters. ASOs降低叙利亚金仓鼠的SARS-CoV-2病毒滴度。

IF 6.1 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2025-08-14 eCollection Date: 2025-09-09 DOI: 10.1016/j.omtn.2025.102653

John J Rossi

引用次数: 0

Pharmacometric modeling of lipid nanoparticle-encapsulated mRNA therapeutics and vaccines: A systematic review. 脂质纳米颗粒包封mRNA疗法和疫苗的药理学建模：系统综述。

IF 6.1 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2025-08-14 eCollection Date: 2025-09-09 DOI: 10.1016/j.omtn.2025.102686

Miao Zhang, Linh Van, Mansoor M Amiji

{"title":"Pharmacometric modeling of lipid nanoparticle-encapsulated mRNA therapeutics and vaccines: A systematic review.","authors":"Miao Zhang, Linh Van, Mansoor M Amiji","doi":"10.1016/j.omtn.2025.102686","DOIUrl":"10.1016/j.omtn.2025.102686","url":null,"abstract":"Significant progress has been made in the development of lipid nanoparticle (LNP)-encapsulated messenger RNA (mRNA)-based modalities with numerous candidates entering clinical trials. These novel modalities require the application of innovative quantitative models to inform the development of mRNA-LNP-based candidates. To this end, we conducted a comprehensive search of registered clinical trials related to mRNA-based modalities on ClinicalTrials.gov, summarizing the current advancements of mRNA-LNP-based modalities and their expanding therapeutic applications. Also, we performed a thorough review of quantitative models related to mRNA-LNP-based modalities from PubMed, Google Scholar, and Embase databases, exploring the model structures employed to capture the in vivo processes of mRNA-LNP, along with their current applications. Between 2002 and October 28, 2024, around 189 clinical trials were registered on ClinicalTrials.gov, encompassing approximately 132 unique mRNA-based modalities targeting 18 disease areas. There are 15 studies that have published quantitative models supporting both the preclinical and clinical development of mRNA-LNP-based therapeutics. Detail regarding quantitative modeling of mRNA-LNP, especially absorption, distribution, metabolism, and excretion, as well as the activation processes of immune responses induced by mRNA-LNP-based vaccines are reviewed. Furthermore, we offer insights for future research related to mRNA-LNP-related models, aimed at enhancing predictive performance and facilitating the expedited advancement of mRNA-LNP-related clinical development.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"36 3","pages":"102686"},"PeriodicalIF":6.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular properties and intramolecular interactions of peptide-conjugated phosphorodiamidate morpholino oligonucleotides. 肽偶联磷酸二酯morpholino寡核苷酸的分子性质和分子内相互作用。

IF 6.1 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2025-08-14 eCollection Date: 2025-09-09 DOI: 10.1016/j.omtn.2025.102685

Evgenii Kliuchnikov, Farkhad Maksudov, Daniel Pierson, Kenneth A Marx, Arani Chanda, Valeri Barsegov

{"title":"Molecular properties and intramolecular interactions of peptide-conjugated phosphorodiamidate morpholino oligonucleotides.","authors":"Evgenii Kliuchnikov, Farkhad Maksudov, Daniel Pierson, Kenneth A Marx, Arani Chanda, Valeri Barsegov","doi":"10.1016/j.omtn.2025.102685","DOIUrl":"10.1016/j.omtn.2025.102685","url":null,"abstract":"We combined circular dichroism (CD) and viscosity measurements with molecular dynamics (MD) simulations and classification and regression approaches to machine learning to characterize solution structures of 22-mer, 25-mer, and 30-mer peptide- (-GlyArg6) conjugated phosphorodiamidate morpholino oligonucleotides (PPMOs). PPMO molecules form non-canonical folded structures with 1.4- to 1.5-nm radius of gyration, 4-6 base pairs and 5-11 base stacks, characterized by -49 to -71 kcal/mol free energy of folding. The 4.5-6.1 cm3/g intrinsic viscosity and Huggins constant of 4.5-9.7 indicate PPMO-PPMO interactions at higher concentrations. The random-coil 3'-end conjugated -GlyArg6 portion does not alter molecular properties of phosphorodiamidate morpholino oligonucleotide (PMO) components, which explains why CD spectra, viscosity-concentration profiles, and inhibitor activities of 22-mer, 25-mer, and 30-mer PPMOs and PMOs are similar but the peptide enhances the PPMO cellular uptake. PPMOs' viscosity is lower than PMOs' viscosity, due to PMO-peptide position-dependent interactions, especially in 25-mer PPMO, explaining differences in CD and high-concentration viscosity. These results reiterate the importance of the conformational ensemble view of non-canonical PPMO structures in solution, in agreement with our previous PMO study. The addition of -GlyArg6 does not alter the structure and molecular properties of the PMO components of the PPMO structures but impacts the viscosity of the PPMO-based aqueous solution formulations.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"36 3","pages":"102685"},"PeriodicalIF":6.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Implications of circular transcripts in DM1 pathomechanism. 环状转录本在DM1病理机制中的意义。

IF 6.1 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2025-08-13 eCollection Date: 2025-09-09 DOI: 10.1016/j.omtn.2025.102661

Marzena Wojciechowska, Piotr Kozlowski

引用次数: 0

Epigenetic small molecule screening identifies a new HDACi compound for ameliorating Duchenne muscular dystrophy. 表观遗传小分子筛选鉴定一种新的HDACi化合物改善杜氏肌营养不良症。

IF 6.1 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2025-08-13 eCollection Date: 2025-09-09 DOI: 10.1016/j.omtn.2025.102683

Ke'ale W Louie, Eva H Hasegawa, Gist H Farr, Amanda C Ignacz, Alison Paguio, Alyssa Maenza, Alison G Paquette, Clarissa A Henry, Lisa Maves

{"title":"Epigenetic small molecule screening identifies a new HDACi compound for ameliorating Duchenne muscular dystrophy.","authors":"Ke'ale W Louie, Eva H Hasegawa, Gist H Farr, Amanda C Ignacz, Alison Paguio, Alyssa Maenza, Alison G Paquette, Clarissa A Henry, Lisa Maves","doi":"10.1016/j.omtn.2025.102683","DOIUrl":"10.1016/j.omtn.2025.102683","url":null,"abstract":"Duchenne muscular dystrophy (DMD) is the most common inherited muscle disease. There are currently few effective therapies to treat the disease, although many approaches are being pursued. Certain histone deacetylase inhibitors (HDACi) have been shown to ameliorate DMD phenotypes in mouse and zebrafish models, and the HDACi givinostat has recently gained FDA approval for DMD. Our goal was to identify additional HDACi, or other classes of epigenetic small molecules, that are beneficial for DMD. Using an established animal model for DMD, the zebrafish dmd mutant strain sapje, we screened a library of over 800 epigenetic small molecules. Our screening identified a new HDACi, SR-4370, that ameliorated dmd mutant zebrafish skeletal muscle degeneration, as well as additional HDACi that have previously been shown to improve dmd zebrafish. We find that a single early treatment of HDACi can ameliorate the muscle phenotype and increase lifespan in dmd zebrafish. Furthermore, we find that HDACi treatments that improve dmd muscle also cause increased histone acetylation in zebrafish larvae. Our results add to the growing evidence that HDACi are promising candidates for treating DMD. Our study also provides further support for the effectiveness of small molecule screening in dmd zebrafish.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"36 3","pages":"102683"},"PeriodicalIF":6.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

From binary to synergy in precision mRNA therapeutics: Dual-microRNA-sensing mRNAs for modular logic control of protein expression. 从二元到精确mRNA治疗的协同：用于模块化逻辑控制蛋白质表达的双微rna传感mRNA。

IF 6.1 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2025-08-13 eCollection Date: 2025-09-09 DOI: 10.1016/j.omtn.2025.102651

Chermaine Tan, Sherry Aw

引用次数: 0

Dendritic siRNA conjugate riding albumin for targeted delivery to solid tumors. 树突状siRNA结合白蛋白靶向递送到实体肿瘤。

IF 6.1 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2025-08-13 eCollection Date: 2025-09-09 DOI: 10.1016/j.omtn.2025.102657

Brady Wang, Jason T Gatlin, Puneet Anand

引用次数: 0

Erratum: BMAL1-TTK-H2Bub1 loop deficiency contributes to impaired BM-MSC-mediated bone formation in senile osteoporosis. 勘误表：BMAL1-TTK-H2Bub1环缺乏有助于衰老骨质疏松症中bm - msc介导的骨形成受损。

IF 6.1 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2025-08-13 eCollection Date: 2025-09-09 DOI: 10.1016/j.omtn.2025.102638

Li Jinteng, Xu Peitao, Yu Wenhui, Ye Guiwen, Ye Feng, Xu Xiaojun, Su Zepeng, Lin Jiajie, Che Yunshu, Zhang Zhaoqiang, Zeng Yipeng, Li Zhikun, Feng Pei, Cao Qian, Li Dateng, Xie Zhongyu, Wu Yanfeng, Shen Huiyong

引用次数: 0

Analytical approach for identification and mechanistic insights into mRNA-lipid adduct formation. mrna -脂质加合物形成的鉴定和机理分析方法。

IF 6.1 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2025-08-13 eCollection Date: 2025-09-09 DOI: 10.1016/j.omtn.2025.102684

Sebastien Peronin, Camille Malburet, Chamsan Daher-Hassan, Christelle Picard, Thibaut Willemin, Federica Costamagna, Luc Even, Thierry Eynard, Fethi Bensaid, Stéphanie Fertier-Prizzon, Marc Francois-Heude

{"title":"Analytical approach for identification and mechanistic insights into mRNA-lipid adduct formation.","authors":"Sebastien Peronin, Camille Malburet, Chamsan Daher-Hassan, Christelle Picard, Thibaut Willemin, Federica Costamagna, Luc Even, Thierry Eynard, Fethi Bensaid, Stéphanie Fertier-Prizzon, Marc Francois-Heude","doi":"10.1016/j.omtn.2025.102684","DOIUrl":"10.1016/j.omtn.2025.102684","url":null,"abstract":"Messenger ribonucleic acid (mRNA), a promising tool in vaccine and therapeutic development, is reliant on intact mRNA delivery into target cells. Given its susceptibility to degradation, ensuring its stability is crucial, necessitating rigorous quality control throughout the product life cycle. This study presents an ion-pair reverse-phase liquid chromatography method that enables rapid and direct mRNA extraction from lipid nanoparticles, facilitated by using a surfactant in the sample preparation. This method, optimized using design of experiments (DoE), allows relative quantification of intact mRNA, mRNA fragments, and mRNA-lipid adducts. Forced degradation studies were used to investigate the impact of mRNA-lipid adducts on protein expression and to identify their chemical structures. The structures, identified by mass spectrometry, suggest reaction mechanisms that differ from those described in the literature so far. Further studies evaluated how formulation parameters such as pH, ionic strength, and buffering species affect mRNA-lipid adduct formation and mRNA fragmentation. A DoE assessed the impact of formulation parameters on mRNA integrity and mRNA-lipid adducts, showing that pH plays the major role. Overall, these findings have significant implications for the design and development of future mRNA-based biopharmaceuticals.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"36 3","pages":"102684"},"PeriodicalIF":6.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0