دورية أكاديمية
Anti-HB-EGF Antibody-Mediated Delivery of siRNA to Atherosclerotic Lesions in Mice.
| العنوان: | Anti-HB-EGF Antibody-Mediated Delivery of siRNA to Atherosclerotic Lesions in Mice. |
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| المؤلفون: | Tsuchida S; Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine., Matsuzaki T; Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University., Yamato M; Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine., Okuda K; Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine., Fu HY; Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine., Araki R; Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine., Sanada S; Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine., Asanuma H; Department of Internal Medicine, Meiji University of Integrative Medicine., Asano Y; Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine., Asakura M; Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine., Hao H; Department of Pathology, Nihon University School of Medicine., Takashima S; Department of Medical Biochemistry, Osaka University Graduate School of Medicine., Kitakaze M; Clinical Research and Development, National Cerebral and Cardiovascular Center Research Institute., Sakata Y; Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine., Mekada E; Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University., Minamino T; Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University. |
| المصدر: | International heart journal [Int Heart J] 2018 Nov 28; Vol. 59 (6), pp. 1425-1431. Date of Electronic Publication: 2018 Nov 05. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: International Heart Journal Association Country of Publication: Japan NLM ID: 101244240 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1349-3299 (Electronic) Linking ISSN: 13492365 NLM ISO Abbreviation: Int Heart J Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Tokyo, Japan] : International Heart Journal Association, [2005]- |
| مواضيع طبية MeSH: | Antibodies/*therapeutic use , Atherosclerosis/*therapy , Avidin/*immunology , Genetic Therapy/*methods , Heparin-binding EGF-like Growth Factor/*immunology , RNA, Small Interfering/*therapeutic use, Animals ; Atherosclerosis/metabolism ; Humans ; Mice ; Mice, Knockout ; Treatment Outcome |
| مستخلص: | For atherosclerotic cardiovascular diseases (ACD), gene therapy may be a potential therapeutic strategy; however, lack of effective and safe methods for gene delivery to atherosclerotic plaques have limited its potential therapeutic applications. To overcome this limitation, we developed a novel antibody-based gene delivery system (anti-HB-EGF/NA vector) by chemically crosslinking antibodies against human heparin-binding epidermal growth factor-like growth factor (HB-EGF). It has been shown to be excessively expressed in human atherosclerotic plaques and NeutrAvidin (NA) for conjugating biotinylated siRNA. Immunofluorescence staining and quantitative flow cytometry analysis using human HB-EGF-expressing cells showed both antibody-mediated selective cellular targeting and efficient intracellular delivery of conjugated biotin-fluorescence. Moreover, we demonstrated antibody-mediated significant and selective gene knockdown via conjugation with anti-HB-EGF/NA vector and biotinylated siRNA (anti-HB-EGF/NA/b-siRNA) in vitro. Furthermore, using high fat-fed human HB-EGF knock-in and apolipoprotein E-knockout (Hbegf hz/hz; Apoe-/-) mice, we demonstrated that the anti-HB-EGF/NA vector, conjugating biotin-fluorescence, increasingly accumulated within the atherosclerotic plaques of the ascending aorta in which human HB-EGF expression levels were highly elevated. Moreover, in response to a single intravenous injection of anti-HB-EGF/NA/b-siRNA in a dose-dependent manner, qPCR analysis of laser-dissected atherosclerotic plaques of the ascending aorta showed significant knockdown of the reporter gene expression. These results suggest that the anti-HB-EGF antibody-mediated siRNA delivery could be a promising delivery system for gene therapy of ACD. |
| فهرسة مساهمة: | Keywords: Atherosclerosis; siRNA delivery |
| المشرفين على المادة: | 0 (Antibodies) 0 (Heparin-binding EGF-like Growth Factor) 0 (RNA, Small Interfering) 0 (neutravidin) 1405-69-2 (Avidin) |
| تواريخ الأحداث: | Date Created: 20181106 Date Completed: 20181212 Latest Revision: 20181212 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1536/ihj.17-644 |
| PMID: | 30393262 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1349-3299 |
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| DOI: | 10.1536/ihj.17-644 |