Biodistribution and safety profile of recombinant adeno-associated virus serotype 6 vectors following intravenous delivery.
Recombinant adeno-associated virus vectors based on serotype 6 (rAAV6) efficiently transduce skeletal muscle after intravenous administration and have shown efficacy in the mdx model of muscular dystrophy. As a prelude to future clinical studies, we investigated the biodistribution and safety profile of rAAV6 in mice. Although it was present in all organs tested, rAAV6 was sequestered mainly in the liver and spleen. rAAV6 had a minimal effect on circulating blood cells and caused no apparent hepatotoxicity or coagulation activation. rAAV6 caused some neutrophil infiltration into the liver, with a transient elevation in cytokine and chemokine transcription/secretion. In summary, rAAV6 induces transient toxicity that subsides almost completely within 72 h and causes no significant side effects.
Stone
Daniel
D
Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Liu
Ying
Y
Li
Zong-Yi
ZY
Strauss
Robert
R
Finn
Eric E
EE
Allen
James M
JM
Chamberlain
Jeffrey S
JS
Lieber
André
A
D000818:Animals; D001777:Blood Coagulation; D016207:Cytokines / Q000378:metabolism; D000229:Dependovirus; D005822:Genetic Vectors / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008099:Liver / Q000473:pathology / Q000821:virology; D008111:Liver Function Tests; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D013154:Spleen / Q000821:virology
D016207:Cytokines