Widespread tissue delivery of antagomiRs via intramuscular administration.

IF 4.6 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Molecular Therapy-Methods & Clinical Development Pub Date : 2025-05-19 eCollection Date: 2025-06-12 DOI:10.1016/j.omtm.2025.101488

Christodoulos Messios, Andrie Koutsoulidou, Leonidas A Phylactou

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引用次数: 0

Abstract

Muscles, traditionally recognized for their role in locomotion and breathing, also participate in tissue communication. Extracellular microRNAs (miRNA) have been identified as key players in intercellular and inter-organ communication in muscle and other tissues. We have previously shown that intramuscular administration of an antagomiR led to the repression of target miRNA in neighboring skeletal muscles. This study investigated whether antagomiRs could be delivered to distant muscle and other tissues following intramuscular administration. We designed antagomiRs targeting a muscle-specific miRNA, miR-133b; a ubiquitously expressed miRNA, miR-16; and a scrambled oligonucleotide. Although all sequences were detected in neighboring skeletal muscles and distant tissues following intramuscular administration, antagomiR-133b showed the highest accumulation and efficacy in various tissues. This is the first study to provide evidence that intramuscular administration of antagomiRs could be utilized to achieve efficient and widespread distribution in tissues. This in turn could form the basis for alternative future therapeutic approaches.

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安塔戈米通过肌肉给药的广泛组织递送。

肌肉，传统上被认为是运动和呼吸的角色，也参与组织交流。细胞外微小核糖核酸（miRNA）在肌肉和其他组织的细胞间和器官间通讯中起着关键作用。我们之前的研究表明，肌内注射一种安塔哥米可抑制邻近骨骼肌中的靶miRNA。这项研究调查了安塔戈米是否可以在肌内给药后传递到远端肌肉和其他组织。我们设计了针对肌肉特异性miRNA miR-133b的拮抗剂；一个无处不在表达的miRNA miR-16；和一个混乱的寡核苷酸。虽然在肌内给药后，在邻近的骨骼肌和远端组织中检测到所有序列，但antagomiR-133b在各组织中的蓄积和疗效最高。这是第一个提供证据的研究，证明安塔戈米肌内给药可以实现有效和广泛的组织分布。这反过来又可以形成未来替代治疗方法的基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Therapy-Methods & Clinical Development Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

9.90

自引率

4.30%

发文量

163

审稿时长

12 weeks

期刊介绍： The aim of Molecular Therapy—Methods & Clinical Development is to build upon the success of Molecular Therapy in publishing important peer-reviewed methods and procedures, as well as translational advances in the broad array of fields under the molecular therapy umbrella. Topics of particular interest within the journal''s scope include: Gene vector engineering and production, Methods for targeted genome editing and engineering, Methods and technology development for cell reprogramming and directed differentiation of pluripotent cells, Methods for gene and cell vector delivery, Development of biomaterials and nanoparticles for applications in gene and cell therapy and regenerative medicine, Analysis of gene and cell vector biodistribution and tracking, Pharmacology/toxicology studies of new and next-generation vectors, Methods for cell isolation, engineering, culture, expansion, and transplantation, Cell processing, storage, and banking for therapeutic application, Preclinical and QC/QA assay development, Translational and clinical scale-up and Good Manufacturing procedures and process development, Clinical protocol development, Computational and bioinformatic methods for analysis, modeling, or visualization of biological data, Negotiating the regulatory approval process and obtaining such approval for clinical trials.