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.
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Acknowledgements
We thank Drs Guangping Gao and Jim Wilson for providing the AAV-9 packaging plasmid pRep2/Cap9 We thank Drs Lixing Reneker and Bo Lei for the help with retinal embedding and retinal morphology data interpretation. This work is supported by grants from the National Institutes of Health (AR-49419, DD; DK-76522, DD), the Muscular Dystrophy Association (DD) and the Cystic Fibrosis Foundation (DD). BB was partially supported by a training grant from the National Institutes of Health (GM 008396).
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Bostick, B., Ghosh, A., Yue, Y. et al. Systemic AAV-9 transduction in mice is influenced by animal age but not by the route of administration. Gene Ther 14, 1605–1609 (2007). https://doi.org/10.1038/sj.gt.3303029
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DOI: https://doi.org/10.1038/sj.gt.3303029
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