title: Liquid jet delivery method featuring S100A1 gene therapy in the rodent model following acute myocardial infarction.
abstract: 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 × 10¹¹ viral particles). For each post MI rat, the LJ device fired three separate 100 μl 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.
authors.affiliation: Department of Thoracic and Cardiac Surgery, Sanger Heart and Vascular Institute, Carolinas HealthCare System, Charlotte, NC, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Fargnoli
authors.affiliation: Department of Thoracic and Cardiac Surgery, Sanger Heart and Vascular Institute, Carolinas HealthCare System, Charlotte, NC, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Katz
authors.affiliation: Department of Thoracic and Cardiac Surgery, Sanger Heart and Vascular Institute, Carolinas HealthCare System, Charlotte, NC, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Williams
authors.affiliation: Department of Thoracic and Cardiac Surgery, Sanger Heart and Vascular Institute, Carolinas HealthCare System, Charlotte, NC, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Kendle
authors.affiliation: Molecular Biology Core, Department of Therapeutic Research and Development, Cannon Research Center, Carolinas HealthCare System, Charlotte, NC, USA.
authors.forename: N
authors.initials: N
authors.lastname: Steuerwald
authors.affiliation: Department of Thoracic and Cardiac Surgery, Sanger Heart and Vascular Institute, Carolinas HealthCare System, Charlotte, NC, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Bridges
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D008297:Male; D009203:Myocardial Infarction / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D009418:S100 Proteins / Q000096:biosynthesis / Q000235:genetics*; D016277:Ventricular Function, Left
chemical_list: D009418:S100 Proteins; C110294:S100A1 protein