Widespread tissue delivery of antagomiRs via intramuscular administration

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 intram...

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Main Authors: Christodoulos Messios, Andrie Koutsoulidou, Leonidas A. Phylactou
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Molecular Therapy: Methods & Clinical Development
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Online Access:http://www.sciencedirect.com/science/article/pii/S232905012500083X
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author Christodoulos Messios
Andrie Koutsoulidou
Leonidas A. Phylactou
author_facet Christodoulos Messios
Andrie Koutsoulidou
Leonidas A. Phylactou
author_sort Christodoulos Messios
collection DOAJ
description 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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spelling doaj-art-1796bc0ba1894b91ae1f2cbf4cd2622a2025-08-20T03:22:22ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012025-06-0133210148810.1016/j.omtm.2025.101488Widespread tissue delivery of antagomiRs via intramuscular administrationChristodoulos Messios0Andrie Koutsoulidou1Leonidas A. Phylactou2Department of Molecular Genetics, Function & Therapy, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, CyprusDepartment of Molecular Genetics, Function & Therapy, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, CyprusDepartment of Molecular Genetics, Function & Therapy, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, Cyprus; Corresponding author: Leonidas A. Phylactou, Department of Molecular Genetics, Function & Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus.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.http://www.sciencedirect.com/science/article/pii/S232905012500083Xskeletal muscleoligonucleotidesmiRNAantagomiRsystemic administrationgene therapy
spellingShingle Christodoulos Messios
Andrie Koutsoulidou
Leonidas A. Phylactou
Widespread tissue delivery of antagomiRs via intramuscular administration
Molecular Therapy: Methods & Clinical Development
skeletal muscle
oligonucleotides
miRNA
antagomiR
systemic administration
gene therapy
title Widespread tissue delivery of antagomiRs via intramuscular administration
title_full Widespread tissue delivery of antagomiRs via intramuscular administration
title_fullStr Widespread tissue delivery of antagomiRs via intramuscular administration
title_full_unstemmed Widespread tissue delivery of antagomiRs via intramuscular administration
title_short Widespread tissue delivery of antagomiRs via intramuscular administration
title_sort widespread tissue delivery of antagomirs via intramuscular administration
topic skeletal muscle
oligonucleotides
miRNA
antagomiR
systemic administration
gene therapy
url http://www.sciencedirect.com/science/article/pii/S232905012500083X
work_keys_str_mv AT christodoulosmessios widespreadtissuedeliveryofantagomirsviaintramuscularadministration
AT andriekoutsoulidou widespreadtissuedeliveryofantagomirsviaintramuscularadministration
AT leonidasaphylactou widespreadtissuedeliveryofantagomirsviaintramuscularadministration