Improved cardiac-specific delivery of RAGE siRNA within small extracellular vesicles engineered to express intense cardiac targeting peptide attenuates myocarditis
Small extracellular vesicles (sEVs) are nanometer-sized membranous vesicles secreted by cells, with important roles in physiological and pathological processes. Recent research has established the application of sEVs as therapeutic vehicles in various conditions, including heart disease. However, th...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-06-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253121001128 |
| _version_ | 1818929973407252480 |
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| author | Hyoeun Kim Dasom Mun Ji-Young Kang Seung-Hyun Lee Nuri Yun Boyoung Joung |
| author_facet | Hyoeun Kim Dasom Mun Ji-Young Kang Seung-Hyun Lee Nuri Yun Boyoung Joung |
| author_sort | Hyoeun Kim |
| collection | DOAJ |
| description | Small extracellular vesicles (sEVs) are nanometer-sized membranous vesicles secreted by cells, with important roles in physiological and pathological processes. Recent research has established the application of sEVs as therapeutic vehicles in various conditions, including heart disease. However, the high risk of off-target effects is a major barrier for their introduction into the clinic. This study evaluated the use of modified sEVs expressing high levels of cardiac-targeting peptide (CTP) for therapeutic small interfering RNA (siRNA) delivery in myocarditis, an inflammatory disease of heart. sEVs were extracted from the cell culture medium of HEK293 cells stably expressing CTP-LAMP2b (referred to as C-sEVs). The cardiac targeting ability of C-sEVs with the highest CTP-LAMP2b expression was >2-fold greater than that of normal sEVs (N-sEVs). An siRNA targeting the receptor for advanced glycation end products (RAGE) (siRAGE) was selected as a therapeutic siRNA and loaded into C-sEVs. The efficiency of cardiac-specific siRNA delivery via C-sEVs was >2-fold higher than that via N-sEVs. Furthermore, siRAGE-loaded C-sEVs attenuated inflammation in both cell culture and an in vivo model of myocarditis. Taken together, C-sEVs may be a useful drug delivery vehicle for the treatment of heart disease. |
| first_indexed | 2024-12-20T03:53:18Z |
| format | Article |
| id | doaj.art-5120cedaa63d4a62a422f0793d41c06a |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-20T03:53:18Z |
| publishDate | 2021-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-5120cedaa63d4a62a422f0793d41c06a2022-12-21T19:54:24ZengElsevierMolecular Therapy: Nucleic Acids2162-25312021-06-012410241032Improved cardiac-specific delivery of RAGE siRNA within small extracellular vesicles engineered to express intense cardiac targeting peptide attenuates myocarditisHyoeun Kim0Dasom Mun1Ji-Young Kang2Seung-Hyun Lee3Nuri Yun4Boyoung Joung5Division of Cardiology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, Republic of KoreaDivision of Cardiology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, Republic of KoreaDivision of Cardiology, Yonsei University College of Medicine, Seoul 03722, Republic of KoreaDepartment of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul 03722, Republic of KoreaInstitute of Life Science & Biotechnology, Yonsei University, Seoul 03722, Republic of Korea; Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 03722, Republic of Korea; Corresponding author: Nuri Yun, PhD, Institute of Life Science & Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.Division of Cardiology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, Republic of Korea; Corresponding author: Boyoung Joung, MD, PhD, Division of Cardiology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.Small extracellular vesicles (sEVs) are nanometer-sized membranous vesicles secreted by cells, with important roles in physiological and pathological processes. Recent research has established the application of sEVs as therapeutic vehicles in various conditions, including heart disease. However, the high risk of off-target effects is a major barrier for their introduction into the clinic. This study evaluated the use of modified sEVs expressing high levels of cardiac-targeting peptide (CTP) for therapeutic small interfering RNA (siRNA) delivery in myocarditis, an inflammatory disease of heart. sEVs were extracted from the cell culture medium of HEK293 cells stably expressing CTP-LAMP2b (referred to as C-sEVs). The cardiac targeting ability of C-sEVs with the highest CTP-LAMP2b expression was >2-fold greater than that of normal sEVs (N-sEVs). An siRNA targeting the receptor for advanced glycation end products (RAGE) (siRAGE) was selected as a therapeutic siRNA and loaded into C-sEVs. The efficiency of cardiac-specific siRNA delivery via C-sEVs was >2-fold higher than that via N-sEVs. Furthermore, siRAGE-loaded C-sEVs attenuated inflammation in both cell culture and an in vivo model of myocarditis. Taken together, C-sEVs may be a useful drug delivery vehicle for the treatment of heart disease.http://www.sciencedirect.com/science/article/pii/S2162253121001128small extracellular vesiclescardiac-targeting peptideheart-specific deliverysmall interfering RNAmyocarditis |
| spellingShingle | Hyoeun Kim Dasom Mun Ji-Young Kang Seung-Hyun Lee Nuri Yun Boyoung Joung Improved cardiac-specific delivery of RAGE siRNA within small extracellular vesicles engineered to express intense cardiac targeting peptide attenuates myocarditis Molecular Therapy: Nucleic Acids small extracellular vesicles cardiac-targeting peptide heart-specific delivery small interfering RNA myocarditis |
| title | Improved cardiac-specific delivery of RAGE siRNA within small extracellular vesicles engineered to express intense cardiac targeting peptide attenuates myocarditis |
| title_full | Improved cardiac-specific delivery of RAGE siRNA within small extracellular vesicles engineered to express intense cardiac targeting peptide attenuates myocarditis |
| title_fullStr | Improved cardiac-specific delivery of RAGE siRNA within small extracellular vesicles engineered to express intense cardiac targeting peptide attenuates myocarditis |
| title_full_unstemmed | Improved cardiac-specific delivery of RAGE siRNA within small extracellular vesicles engineered to express intense cardiac targeting peptide attenuates myocarditis |
| title_short | Improved cardiac-specific delivery of RAGE siRNA within small extracellular vesicles engineered to express intense cardiac targeting peptide attenuates myocarditis |
| title_sort | improved cardiac specific delivery of rage sirna within small extracellular vesicles engineered to express intense cardiac targeting peptide attenuates myocarditis |
| topic | small extracellular vesicles cardiac-targeting peptide heart-specific delivery small interfering RNA myocarditis |
| url | http://www.sciencedirect.com/science/article/pii/S2162253121001128 |
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