A Needleless Liquid Jet Injection Delivery Method for Cardiac Gene Therapy: a Comparative Evaluation Versus Standard Routes of Delivery Reveals Enhanced Therapeutic Retention and Cardiac Specific Gene Expression

This study evaluates needleless liquid jet method and compares it with three common experimental methods: (1) intramuscular injection (IM), (2) left ventricular intracavitary infusion (LVIC), and (3) LV intracavitary infusion with aortic and pulmonary occlusion (LVIC-OCCL). Two protocols were executed. First (n = 24 rats), retention of dye was evaluated 10 min after delivery in an acute model. The acute study revealed the following: significantly higher dye retention (expressed as % myocardial cross-section area) in the left ventricle in both the liquid jet [52 +/- 4] % and LVIC-OCCL [58 +/- 3] % groups p < 0.05 compared with IM [31 +/- 8] % and LVIC [35 +/- 4] %. In the second (n = 16 rats), each animal received adeno-associated virus encoding green fluorescent protein (AAV.EGFP) at a single dose with terminal 6-week endpoint. In the second phase with AAV.EGFP at 6 weeks post-delivery, a similar trend was found with liquid jet [54 +/- 5] % and LVIC-OCCL [60 +/- 8] % featuring more LV expression as compared with IM [30 +/- 9] % and LVIC [23 +/- 9] %. The IM and LVIC-OCCL cross sections revealed myocardial fibrosis. With more detailed development in future model studies, needleless liquid jet delivery offers a promising strategy to improve direct myocardial delivery.