¹Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO, USA

Correspondence: Dr D Duan, Department of Molecular Microbiology and Immunology, University of Missouri, School of Medicine, M610G Med. Sci. Building, One Hospital Dr, Columbia, MO 65212, USA. E-mail: duand@missouri.edu

Received 21 May 2007; Revised 14 August 2007; Accepted 15 August 2007; Published online 27 September 2007.

Abstract

Adeno-associated virus (AAV) serotype-9 (AAV-9) has attracted great attention as an optimal vehicle for body-wide gene delivery. Here we examined the effect of animal age (newborn vs adult) and the route of administration (intravenous vs intra-arterial) on systemic AAV-9 transduction. We delivered an alkaline phosphatase (AP) reporter gene AAV vector (AV.RSV.AP) to either newborn (via either the facial vein or the left ventricular cavity) or adult (via tail vein) C57Bl/10 mice. At 12 weeks' postinfection, we examined the AP expression. We observed efficient transduction in multiple skeletal muscles and the heart, irrespective of the age or delivery route. However, the soleus muscle, which consists mainly of slow-twitch myofibers, was poorly transduced. Besides striated muscle, we also found consistent high-level transduction in the lung. Abundant AP-positive cells were seen in alveolar cells and vasculature, but not in bronchioles. Interestingly, several organs demonstrated an age-dependent profile. In particular, the aorta, liver and kidney were preferentially transduced in adult mice while the inner layer of retina was strongly transduced only following the neonatal administration. Taken together, our results demonstrate the robustness of intravascular AAV-9 delivery for muscle and lung gene therapy applications. The unique expression patterns in the aorta, liver, kidney and retina call for special attention when designing AAV-9 gene therapy applications for these organs.