A single intravenous injection of adeno-associated virus serotype-9 leads to whole body skeletal muscle transduction in dogs.
The success of many gene therapy applications hinges on efficient whole body transduction. In the case of muscular dystrophies, a therapeutic vector has to reach every muscle in the body. Recent studies suggest that vectors based on adeno-associated virus (AAV) are capable of body-wide transduction in rodents. However, translating this finding to large animals remains a challenge. Here we explored systemic gene delivery with AAV serotype-9 (AAV-9) in neonatal dogs. Previous attempts to directly deliver AAV to adult canine muscle have yielded minimal transduction due to a strong cellular immune response. However, in neonatal dogs we observed robust skeletal muscle transduction throughout the body after a single intravenous injection. Importantly, systemic transduction was achieved in the absence of pharmacological intervention or immune suppression and it lasted for at least 6 months (the duration of study). We also observed several unique features not predicted by murine studies. In particular, cardiac muscle was barely transduced in dogs. Many muscular dystrophy patients can be identified by neonatal screening. The technology described here may lead to an effective early intervention in these patients.
Yue
Yongping
Y
Department of Molecular Microbiology and Immunology, School of Medicine, The University of Missouri, Columbia, Missouri 65212, USA.
Ghosh
Arkasubhra
A
Long
Chun
C
Bostick
Brian
B
Smith
Bruce F
BF
Kornegay
Joe N
JN
Duan
Dongsheng
D
D000818:Animals; D000831:Animals, Newborn; D000229:Dependovirus / Q000235:genetics* / Q000276:immunology; D004285:Dogs; D005822:Genetic Vectors / Q000235:genetics; D007275:Injections, Intravenous; D008833:Microcirculation; D018482:Muscle, Skeletal / Q000276:immunology / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics*