Liquid jet delivery method featuring S100A1 gene therapy in the rodent model following acute myocardial infarction

The S100A1 gene is a promising target enhancing contractility and survival post myocardial infarction (MI). Achieving sufficient gene delivery within safety limits is a major translational problem. This proof of concept study evaluates viral mediated S100A1 overexpression featuring a novel liquid jet delivery (LJ) method. Twenty-four rats after successful MI were divided into three groups (n = 8 ea.): saline control (SA); ssAAV9. S100A1 (SS) delivery; and scAAV9. S100A1 (SC) delivery (both 1.2 x 10(11) viral particles). For each post MI rat, the LJ device fired three separate 100 mu l injections into the myocardium. Following 10 weeks, all rats were evaluated with echocardiography, quantitative PCR (qPCR) and overall S100A1 and CD38 immune protein. At 10 weeks all groups demonstrated a functional decline from baseline, but the S100A1 therapy groups displayed preserved left ventricular function with significantly higher ejection fraction %; SS group (60 +/- 3) and SC group (57 +/- 4) versus saline (46 +/- 3), P < 0.05. Heart qPCR testing showed robust S100A1 in the SS (10 147 +/- 3993) and SC (35 155 +/- 5808) copies per 100 ng DNA, while off-target liver detection was lower in both SS (40 +/- 40), SC (34 841 +/- 3164), respectively. Cardiac S100A1 protein expression was (4.3 +/- 0.2) and (6.1 +/- 0.3) fold higher than controls in the SS and SC groups, respectively, P < 0.05.