Delivering LINE1 antisense oligonucleotides via endothelial targeting extracellular vesicles to ameliorate myocardial infarction-induced cardiac senescence
Transposable elements (TEs) constitute a significant portion of the nuclear genome, but their influence on and ability to manage their activity during tissue regeneration remain largely unknown. Here, we revealed that LINE1, the most abundant TE, responds to cardiomyocyte injury and is overexpressed...
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KeAi Communications Co., Ltd.
2025-11-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X25003019 |
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| author | Enze Fu Kai Pan Benjamin Hinnant Shang Chen Zhibo Han Zhikun Guo Zhong-chao Han Qiong Li Zongjin Li |
| author_facet | Enze Fu Kai Pan Benjamin Hinnant Shang Chen Zhibo Han Zhikun Guo Zhong-chao Han Qiong Li Zongjin Li |
| author_sort | Enze Fu |
| collection | DOAJ |
| description | Transposable elements (TEs) constitute a significant portion of the nuclear genome, but their influence on and ability to manage their activity during tissue regeneration remain largely unknown. Here, we revealed that LINE1, the most abundant TE, responds to cardiomyocyte injury and is overexpressed in a myocardial infarction (MI) model. We developed selectin binding peptide (SBP)-engineered extracellular vesicles (EVs) with targeted functions, which are loaded with LINE1 antisense oligonucleotide (ASO). The engineered EVs display targeted accumulation in injured hearts and protect against myocardial senescence by inhibiting the cGAS-STING‐TBK1‐IRF3 pathway and suppressing the expression of senescence-associated secretory phenotype (SASP) factors. Our data revealed that LINE1 retrotransposon activation is triggered by cardiomyocyte injury in the MI model. We also propose a strategy to reduce cardiomyocyte senescence post-myocardial infarction by modulating LINE1 activity. |
| format | Article |
| id | doaj-art-ca6362e96cc241a2b77ec788482d6c20 |
| institution | Kabale University |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-11-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-ca6362e96cc241a2b77ec788482d6c202025-08-20T03:33:38ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-11-0153587110.1016/j.bioactmat.2025.07.008Delivering LINE1 antisense oligonucleotides via endothelial targeting extracellular vesicles to ameliorate myocardial infarction-induced cardiac senescenceEnze Fu0Kai Pan1Benjamin Hinnant2Shang Chen3Zhibo Han4Zhikun Guo5Zhong-chao Han6Qiong Li7Zongjin Li8Henan Key Laboratory of Cardiac Remodeling and Transplantation, Zhengzhou Seventh People's Hospital, Zhengzhou, 450016, China; School of Medicine, Nankai University, Tianjin, 300071, ChinaSchool of Medicine, Nankai University, Tianjin, 300071, ChinaDivision of Biological Sciences, University of California San Diego, USASchool of Medicine, Nankai University, Tianjin, 300071, ChinaAcademy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300071, China; Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, National Engineering Research Center for Cell Products, AmCellGene Co., Ltd., Tianjin 300457, ChinaHenan Key Laboratory of Cardiac Remodeling and Transplantation, Zhengzhou Seventh People's Hospital, Zhengzhou, 450016, ChinaTianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, National Engineering Research Center for Cell Products, AmCellGene Co., Ltd., Tianjin 300457, ChinaHenan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, 453003, China; North Henan Medical University, Xinxiang, 453003, ChinaHenan Key Laboratory of Cardiac Remodeling and Transplantation, Zhengzhou Seventh People's Hospital, Zhengzhou, 450016, China; School of Medicine, Nankai University, Tianjin, 300071, China; North Henan Medical University, Xinxiang, 453003, China; National Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing 100853, China; Corresponding author.School of Medicine, Nankai University, 94 Weijin Road, Tianjin, 300071, ChinaTransposable elements (TEs) constitute a significant portion of the nuclear genome, but their influence on and ability to manage their activity during tissue regeneration remain largely unknown. Here, we revealed that LINE1, the most abundant TE, responds to cardiomyocyte injury and is overexpressed in a myocardial infarction (MI) model. We developed selectin binding peptide (SBP)-engineered extracellular vesicles (EVs) with targeted functions, which are loaded with LINE1 antisense oligonucleotide (ASO). The engineered EVs display targeted accumulation in injured hearts and protect against myocardial senescence by inhibiting the cGAS-STING‐TBK1‐IRF3 pathway and suppressing the expression of senescence-associated secretory phenotype (SASP) factors. Our data revealed that LINE1 retrotransposon activation is triggered by cardiomyocyte injury in the MI model. We also propose a strategy to reduce cardiomyocyte senescence post-myocardial infarction by modulating LINE1 activity.http://www.sciencedirect.com/science/article/pii/S2452199X25003019Transposable elements (TEs)LINE1 retrotransposonMyocardial infarctionSelectinsExtracellular vesiclesEndothelial cell |
| spellingShingle | Enze Fu Kai Pan Benjamin Hinnant Shang Chen Zhibo Han Zhikun Guo Zhong-chao Han Qiong Li Zongjin Li Delivering LINE1 antisense oligonucleotides via endothelial targeting extracellular vesicles to ameliorate myocardial infarction-induced cardiac senescence Bioactive Materials Transposable elements (TEs) LINE1 retrotransposon Myocardial infarction Selectins Extracellular vesicles Endothelial cell |
| title | Delivering LINE1 antisense oligonucleotides via endothelial targeting extracellular vesicles to ameliorate myocardial infarction-induced cardiac senescence |
| title_full | Delivering LINE1 antisense oligonucleotides via endothelial targeting extracellular vesicles to ameliorate myocardial infarction-induced cardiac senescence |
| title_fullStr | Delivering LINE1 antisense oligonucleotides via endothelial targeting extracellular vesicles to ameliorate myocardial infarction-induced cardiac senescence |
| title_full_unstemmed | Delivering LINE1 antisense oligonucleotides via endothelial targeting extracellular vesicles to ameliorate myocardial infarction-induced cardiac senescence |
| title_short | Delivering LINE1 antisense oligonucleotides via endothelial targeting extracellular vesicles to ameliorate myocardial infarction-induced cardiac senescence |
| title_sort | delivering line1 antisense oligonucleotides via endothelial targeting extracellular vesicles to ameliorate myocardial infarction induced cardiac senescence |
| topic | Transposable elements (TEs) LINE1 retrotransposon Myocardial infarction Selectins Extracellular vesicles Endothelial cell |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X25003019 |
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