Posttranslational control of a cardiac ion channel transgene in vivo: Clarithromycin-hMiRP1-Q9E interactions

Itay Perlstein, Denise Y. Burton, Kenneth Ryan, Suzanne DeFelice, Erin Simmers, Barry Campbell, Jeanne M. Connolly, Amnon Hoffman, Robert J. Levy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


The present study investigates a novel gene therapy approach for atrial arrhythmias, using a clarithromycin-responsive ion channel subunit mutation, hMiRP1-Q9E, cloned into an expression plasmid; wild-type expression plasmids encoding human minK-related protein 1 (HMiRP1) were also used as controls. In a series of pig studies, right atrial myocardium was injected at one site with hMiRP1-Q9E plasmid DNA; a separate site in the same right atrium was injected with wild-type plasmid or was sham injected. Two weeks after transfection intravenous clarithromycin administration resulted in a site-specific, dose-dependent prolongation of the repolarization phase of the right atrial epicardial monophasic action potential (MAP) only at the hMiRP-Q9E sites, but not at sham or wild-type sites. MAP recordings before clarithromycin administration did not differ between hMiRP1-Q9E and control sites. These studies show that regional control of atrial myocardial repolarization by site-specific transfection with plasmid DNA encoding an antibiotic-responsive ion channel subunit is feasible and, because hMiRP1-Q9E-transfected sites were affected only if clarithromycin was given, provide proof of concept for a posttranslational, controllable gene therapy strategy for atrial arrhythmias.

Original languageAmerican English
Pages (from-to)906-910
Number of pages5
JournalHuman Gene Therapy
Issue number7
StatePublished - Jul 2005


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