Table 1.

Delivery Techniques for Gene Therapy

Gene Delivery Technique	Pro	Con
Myocardial injection24	●High density of gene transfer limited to cardiac muscle ●Simple and safe, able to inject percutaneously	●Small area of gene expression ●Multiple injection sites needed ●Acute inflammatory response and potential scarring from the injection
Coronary perfusion‐anterograde and retrograde perfusion	●Delivers genes globally across the myocardium ●Distributes gene vector more homogeneously ●Cardiac specific	●Inefficient ●Delivered into systemic circulation
Aortic cross‐clamp LV cavity infusion4	●Increased gene transfer efficiency	●Accessibility, need open chest ●High risk of myocardial injury ●Not cardiac specific
Cardiopulmonary bypass perfusion and “closed‐loop” system25	●Specifically enhances coronary perfusion by separating it from systemic circulation ●Allows for temperature control of solution, cold increased transfection efficiency ●Increased contact time with gene vector through multiple‐pass cardiac recirculation	●Significant morbidity risk from cardiopulmonary bypass procedure (CBP) ●Intended for patients undergoing CBP
Epicardial painting23	●Cardiac specific ●Complete transmural penetration (atrial) ●High degree of gene transfer	●Accessibility, currently needs open chest
Ultrasound and microbubbles26	●Increased permeability of capillary and cell membrane	●Only slightly improved gene transfer efficiency from myocardial injection alone
Electroporation27	●Enhanced transfer of naked DNA via myocardial injection and retrograde perfusion ●Cardiac specific	●Pulse needs to be delivered in sync or ventricular fibrillation occurs

LV indicates left ventricle.