miR-25 Tough Decoy Enhances Cardiac Function in Heart Failure
- Authors
- Jeong, Dongtak; Yoo, Jimeen; Lee, Philyoung; Kepreotis, Sacha, V; Lee, Ahyoung; Wahlquist, Christine; Brown, Brian D.; Kho, Changwon; Mercola, Mark; Hajjar, Roger J.
- Issue Date
- Mar-2018
- Publisher
- CELL PRESS
- Keywords
- AAV9; calcium signaling; gene therapy; heart failure; miR-25; miRNA; SERCA2a; Tough Decoy; TuD
- Citation
- MOLECULAR THERAPY, v.26, no.3, pp.718 - 729
- Indexed
- SCIE
SCOPUS
- Journal Title
- MOLECULAR THERAPY
- Volume
- 26
- Number
- 3
- Start Page
- 718
- End Page
- 729
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/6408
- DOI
- 10.1016/j.ymthe.2017.11.014
- ISSN
- 1525-0016
- Abstract
- MicroRNAs are promising therapeutic targets, because their inhibition has the potential to normalize gene expression in diseased states. Recently, our group found that miR-25 is a key SERCA2a regulating microRNA, and we showed that multiple injections of antagomirs against miR-25 enhance cardiac contractility and function through SERCA2a restoration in a murine heart failure model. However, for clinical application, a more stable suppressor of miR-25 would be desirable. Tough Decoy (TuD) inhibitors are emerging as a highly effective method for microRNA inhibition due to their resistance to endonucleolytic degradation, high miRNA binding affinity, and efficient delivery. We generated a miR-25 TuD inhibitor and subcloned it into a cardiotropic AAV9 vector to evaluate its efficacy. The AAV9 TuD showed selective inhibition of miR-25 in vitro cardiornyoblast culture. In vivo, AAV9-miR-25 TuD delivered to the murine pressure-overload heart failure model selectively decreased expression of miR-25, increased levels of SERCA2a protein, and ameliorated cardiac dysfunction and fibrosis. Our data indicate that miR-25 TuD is an effective long-term suppressor of miR-25 and a promising therapeutic candidate to treat heart failure.
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Collections - COLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY > ERICA 의약생명과학과 > 1. Journal Articles
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