Short paper

Tissue specific promoters improve specificity of AAV9 mediated transgene expression following intra-vascular gene delivery in neonatal mice

Christina A Pacak^* , Yoshihisa Sakai^* , Bijoy D Thattaliyath , Cathryn S Mah and Barry J Byrne

Powell Gene Therapy Center, College of Medicine, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610-0266, USA

author email corresponding author email* Contributed equally

Genetic Vaccines and Therapy 2008, 6:13doi:10.1186/1479-0556-6-13

Published:	23 September 2008

Abstract

The AAV9 capsid displays a high natural affinity for the heart following a single intravenous (IV) administration in both newborn and adult mice. It also results in substantial albeit relatively lower expression levels in many other tissues. To increase the overall safety of this gene delivery method we sought to identify which one of a group of promoters is able to confer the highest level of cardiac specific expression and concurrently, which is able to provide a broad biodistribution of expression across both cardiac and skeletal muscle. The in vivo behavior of five different promoters was compared: CMV, desmin (Des), alpha-myosin heavy chain (α-MHC), myosin light chain 2 (MLC-2) and cardiac troponin C (cTnC). Following IV administration to newborn mice, LacZ expression was measured by enzyme activity assays. Results showed that rAAV2/9-mediated gene delivery using the α-MHC promoter is effective for focal transgene expression in the heart and the Des promoter is highly suitable for achieving gene expression in cardiac and skeletal muscle following systemic vector administration. Importantly, these promoters provide an added layer of control over transgene activity following systemic gene delivery.