484. Ultrasound-Mediated Microbubble Destruction and Retroviral Gene Delivery

Abstract

Although precise and stable transgene expression can be achieved by direct injection of naked DNA into skeletal muscle; therapeutic, non-invasive gene therapy for a range of less accessible tissues ultimately requires systemic introduction of a vector with subsequent targeted delivery. Current approaches tend to focus on vector modification to ease entry and intracellular passage. Liposomal or lipid-based delivery of naked DNA increases uptake by reducing electrostatic repulsion and encouraging endocytosis at the cell membrane; however, uptake in the liver and spleen causes vector wastage and undesirable non-target transgene expression. Adenoviral vectors are more efficient, but they share with liposomal methods a transient transgene expression, high non-specific delivery and a tendency to accumulate in the liver, whilst retroviral vectors mediate stable gene delivery but are not easily produced in sufficient quantity; in neither case are efficient techniques for targeted delivery established.