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Gene therapy to inhibit CaMKII in CPVT

Nature Reviews Cardiology volume 16, page 456 (2019)Cite this article

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Cardiomyocyte-selective gene therapy to inhibit Ca2+/calmodulin-dependent protein kinase II (CaMKII) effectively suppresses ventricular arrhythmias in mice with mutations known to cause catecholaminergic polymorphic ventricular tachycardia (CPVT). “Delivery of a CaMKII inhibitory peptide by adeno-associated virus (AAV) represents a novel single-dose gene therapy for CPVT,” summarize the researchers.

A characteristic feature of CPVT is adrenergically triggered arrhythmias. Inhibition of CaMKII, an adrenergically activated kinase, has been identified as a therapeutic approach for CPVT. However, given that CaMKII is essential for brain function, CaMKII must be selectively inhibited in cardiomyocytes. Therefore, the researchers designed an AAV vector containing a potent CaMKII inhibitory peptide (AIP) fused to green fluorescent protein (GFP) and expressed from a cardiomyocyte-selective promoter (AAV9–AIP–GFP).

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  • Bongianino, R. & Priori, S. G. Gene therapy to treat cardiac arrhythmias. Nat. Rev. Cardiol. 12, 531–546 (2015)

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  1. Nature Reviews Cardiology http://www.nature.com/nrcardio/

    Gregory B. Lim

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  1. Gregory B. Lim
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Correspondence to Gregory B. Lim.

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Lim, G.B. Gene therapy to inhibit CaMKII in CPVT. Nat Rev Cardiol 16, 456 (2019). https://doi.org/10.1038/s41569-019-0226-x

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