Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2007-11-6
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0969-7128
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1605-9
pubmed:meshHeading
pubmed-meshheading:17898796-Aging, pubmed-meshheading:17898796-Alkaline Phosphatase, pubmed-meshheading:17898796-Animals, pubmed-meshheading:17898796-Animals, Newborn, pubmed-meshheading:17898796-Aorta, pubmed-meshheading:17898796-Dependovirus, pubmed-meshheading:17898796-Gene Expression, pubmed-meshheading:17898796-Gene Therapy, pubmed-meshheading:17898796-Genetic Vectors, pubmed-meshheading:17898796-Injections, Intra-Arterial, pubmed-meshheading:17898796-Injections, Intravenous, pubmed-meshheading:17898796-Kidney, pubmed-meshheading:17898796-Liver, pubmed-meshheading:17898796-Lung, pubmed-meshheading:17898796-Lung Diseases, pubmed-meshheading:17898796-Mice, pubmed-meshheading:17898796-Mice, Inbred C57BL, pubmed-meshheading:17898796-Muscle Fibers, Fast-Twitch, pubmed-meshheading:17898796-Muscular Diseases, pubmed-meshheading:17898796-Myocardium, pubmed-meshheading:17898796-Retina, pubmed-meshheading:17898796-Transduction, Genetic
pubmed:year
2007
pubmed:articleTitle
Systemic AAV-9 transduction in mice is influenced by animal age but not by the route of administration.
pubmed:affiliation
Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural