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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| Format: | Article |
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Elsevier
2025-06-01
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| 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. |
| format | Article |
| id | doaj-art-1796bc0ba1894b91ae1f2cbf4cd2622a |
| institution | DOAJ |
| issn | 2329-0501 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| 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 |