title: A Needleless Liquid Jet Injection Delivery Approach for Cardiac Gene Therapy.
abstract: Fundamentally, cardiac gene therapy clinical trials have demonstrated that route efficiency is paramount in achieving maximum myocardial expression within safety limits. Gene transfer phenomena are largely influenced by physical transport principles (i.e., pressure, residence time, dispersion trafficking, mechanical resistance) that are independent of therapeutic characteristics. An alternative to intracoronary infusion methods, in an effort to improve efficiency in terms of cardiac specificity, is direct myocardial delivery via surgical injection. Direct injection methods circumvent the blood's immunological components and the cardiac system's native anatomical barriers by directly administering product into the myocardium. In addition, this approach offers the advantage of precise site selection. Two unresolved problems with direct delivery wherein the novel needleless liquid jet approach may resolve are: (1) initial therapeutic retention and (2) subsequent host responses associated with highly focal expression.In this protocol, we present a novel approach to improve direct cardiac gene delivery using a needleless liquid jet methodology. The liquid jet application is essentially a device concept that accelerates and disperses the therapeutic at a targeted myocardial site. The core hypothesis offered is that this approach, with optimized settings, could result in increased therapeutic retention in the initial delivery phase. This would theoretically result in more total myocardial expression per dose while at the same time providing a more homogenous profile around the injection site. Therefore, this would increase efficiency in terms of transduced muscle per delivery site and offer a significant improvement to standard intramuscular injection.
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1030, New York, NY, 10029-6574, USA. anthony.fargnoli@mssm.edu.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fargnoli
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1030, New York, NY, 10029-6574, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Katz
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1030, New York, NY, 10029-6574, USA.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Bridges
mesh_terms: D000818:Animals; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000378:metabolism; D007267:Injections; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009339:Needles; D011300:Preoperative Care; D017207:Rats, Sprague-Dawley
keywords: Cardiac injection; Delivery; Gene transfer; Intramuscular; Liquid jet; Needleless