Abstract
The current status and challenges of RNA interference (RNAi) and microRNA modulation strategies for the treatment of myocardial disorders are discussed and related to the classical gene therapeutic approaches of the past decade. Section 2 summarizes the key issues of current vector technologies which determine if they may be suitable for clinical translation of experimental RNAi or microRNA therapeutic protocols. We then present and discuss examples dealing with the potential of cardiac RNAi therapy. First, an approach to block a key early step in the pathogenesis of a virus-induced cardiomyopathy by RNAi targeting of a cellular receptor for cardiopathogenic viruses (Section 3). Second, an approach to improve cardiac function by RNAi targeting of late pathway of heart failure pathogenesis common to myocardial disorders of multiple etiologies. This strategy is directed at myocardial Ca2+ homeostasis which is disturbed in heart failure due to coronary heart disease, heart valve dysfunction, cardiac inflammation, or genetic defects (Section 4). Whereas the first type of strategies (directed at early pathogenesis) need to be tailor-made for each different type of pathomechanism, the second type (targeting late common pathways) has a much broader range of application. This advantage of the second type of approaches is of key importance since enormous efforts need to be undertaken before any regulatory RNA therapy enters the stage of possible clinical translation. If then the number of patients eligible for this protocol is large, the actual transformation of the experimental therapy into a new therapeutic option of clinical importance is far more likely to occur.
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Keywords
- Fabry Disease
- Adenovirus Infection
- Arrhythmogenic Right Ventricular Dysplasia
- Inflammatory Cardiomyopathy
- Synthetic siRNAs
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Abbreviations
- AAV:
-
Adeno-associated virus
- AdV:
-
Adenovirus
- CAR:
-
Coxsackievirus-adenovirus-receptor
- DCM:
-
Dilated cardiomyopathy
- DCMi:
-
Inflammatory cardiomyopathy
- HF:
-
Heart failure
- miRNA:
-
microRNA
- misiRNA:
-
miRNA-based shRNA
- PLB:
-
Phospholamban
- RNAi:
-
RNA interference
- shRNA:
-
Short hairpin RNA
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Poller, W., Suckau, L., Pinkert, S., Fechner, H. (2008). RNA Interference and MicroRNA Modulation for the Treatment of Cardiac Disorders. In: Erdmann, V.A., Poller, W., Barciszewski, J. (eds) RNA Technologies in Cardiovascular Medicine and Research. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-78709-9_8
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