Development of novel nucleic acid therapy aimed at directly controlling liver fibrosis
Currently, no drugs directly treat liver fibrosis. Previously, we have shown that treatment with miR-29a-3p improved liver fibrosis in a mouse model. To investigate the effectiveness of nucleic acid therapy at a lower dose, a modified nucleic acid was prepared based on miR-29a-3p. The original micro...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253124003251 |
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| author | Tomohiro Umezu Masakatsu Takanashi Koji Fujita Akio Ishikawa Yuichirou Harada Yoshinari Matsumoto Masahiko Kuroda Yoshiki Murakami |
| author_facet | Tomohiro Umezu Masakatsu Takanashi Koji Fujita Akio Ishikawa Yuichirou Harada Yoshinari Matsumoto Masahiko Kuroda Yoshiki Murakami |
| author_sort | Tomohiro Umezu |
| collection | DOAJ |
| description | Currently, no drugs directly treat liver fibrosis. Previously, we have shown that treatment with miR-29a-3p improved liver fibrosis in a mouse model. To investigate the effectiveness of nucleic acid therapy at a lower dose, a modified nucleic acid was prepared based on miR-29a-3p. The original microRNA was changed to an RNA-DNA hybrid structure: the 2′ position of the RNA was modified with a fluorine base, and locked nucleic acid and phosphorothioate were crosslinked (hereafter called modified nucleic acid). In a mouse model of chronic liver disease treated with carbon tetrachloride (CCl4), the inhibitory effect on liver fibrosis was evaluated with oral administration of the modified nucleic acid. The modified nucleic acid was detected in the liver and gastrointestinal tract within 15 min of oral administration. After 5 weeks of stimulation with CCl4, oral administration of the modified nucleic acid for 2 weeks improved liver fibrosis; CCl4 stimulation was continued during this period as well. This treatment also suppressed the worsening of liver fibrosis. We developed a method to improve liver fibrosis orally using nuclease-resistant nucleic acids without using a drug delivery system. This method may be used as a new treatment for inhibiting the progression of liver fibrosis. |
| format | Article |
| id | doaj-art-bd8d594836724232b83660ed9f5bf927 |
| institution | Kabale University |
| issn | 2162-2531 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj-art-bd8d594836724232b83660ed9f5bf9272025-01-11T06:41:11ZengElsevierMolecular Therapy: Nucleic Acids2162-25312025-03-01361102438Development of novel nucleic acid therapy aimed at directly controlling liver fibrosisTomohiro Umezu0Masakatsu Takanashi1Koji Fujita2Akio Ishikawa3Yuichirou Harada4Yoshinari Matsumoto5Masahiko Kuroda6Yoshiki Murakami7Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, JapanDepartment of Medical Technology, School of Life and Environmental Science, Azabu University, 1-17-71, Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252-5201, JapanDepartment of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, JapanDepartment of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, JapanDepartment of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, JapanDepartment of Nutrition, Graduate School of Human Life and Ecology, Osaka Metropolitan University, 3-7-30 Habikino, Habikino-shi, Osaka 583-8555, JapanDepartment of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, JapanDepartment of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan; Faculty of Dentistry, Asahi University, 1851 Hozumi, Muzuho, Gifu 501-0296, Japan; Corresponding author: Yoshiki Murakami MD, PhD, Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.Currently, no drugs directly treat liver fibrosis. Previously, we have shown that treatment with miR-29a-3p improved liver fibrosis in a mouse model. To investigate the effectiveness of nucleic acid therapy at a lower dose, a modified nucleic acid was prepared based on miR-29a-3p. The original microRNA was changed to an RNA-DNA hybrid structure: the 2′ position of the RNA was modified with a fluorine base, and locked nucleic acid and phosphorothioate were crosslinked (hereafter called modified nucleic acid). In a mouse model of chronic liver disease treated with carbon tetrachloride (CCl4), the inhibitory effect on liver fibrosis was evaluated with oral administration of the modified nucleic acid. The modified nucleic acid was detected in the liver and gastrointestinal tract within 15 min of oral administration. After 5 weeks of stimulation with CCl4, oral administration of the modified nucleic acid for 2 weeks improved liver fibrosis; CCl4 stimulation was continued during this period as well. This treatment also suppressed the worsening of liver fibrosis. We developed a method to improve liver fibrosis orally using nuclease-resistant nucleic acids without using a drug delivery system. This method may be used as a new treatment for inhibiting the progression of liver fibrosis.http://www.sciencedirect.com/science/article/pii/S2162253124003251MT: Oligonucleotides: Therapies and Applicationsliver fibrosischronic liver injurymiRNAdrug delivery systemmodified oligonucleotide |
| spellingShingle | Tomohiro Umezu Masakatsu Takanashi Koji Fujita Akio Ishikawa Yuichirou Harada Yoshinari Matsumoto Masahiko Kuroda Yoshiki Murakami Development of novel nucleic acid therapy aimed at directly controlling liver fibrosis Molecular Therapy: Nucleic Acids MT: Oligonucleotides: Therapies and Applications liver fibrosis chronic liver injury miRNA drug delivery system modified oligonucleotide |
| title | Development of novel nucleic acid therapy aimed at directly controlling liver fibrosis |
| title_full | Development of novel nucleic acid therapy aimed at directly controlling liver fibrosis |
| title_fullStr | Development of novel nucleic acid therapy aimed at directly controlling liver fibrosis |
| title_full_unstemmed | Development of novel nucleic acid therapy aimed at directly controlling liver fibrosis |
| title_short | Development of novel nucleic acid therapy aimed at directly controlling liver fibrosis |
| title_sort | development of novel nucleic acid therapy aimed at directly controlling liver fibrosis |
| topic | MT: Oligonucleotides: Therapies and Applications liver fibrosis chronic liver injury miRNA drug delivery system modified oligonucleotide |
| url | http://www.sciencedirect.com/science/article/pii/S2162253124003251 |
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