High-level transgene expression in nonhuman primate liver with novel adeno-associated virus serotypes containing self-complementary genomes.
Adeno-associated virus (AAV) vectors are being considered for in vivo applications of gene therapy in the treatment of a variety of disorders. This study evaluates the biology of second-generation vectors based on the novel serotypes AAV7 and AAV8 and containing self-complementary genomes in the nonhuman primate liver. Stable levels of transgene expression were achieved in cynomolgus macaques and suggest efficiencies at least 2 log higher than what could be achieved with AAV2 vectors using traditional single-stranded genomes. Analysis of DNAs from tissues revealed high levels of vector in the liver that appeared proportional to the relative amounts of transgene expression.
Gao
Guang-Ping
GP
Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-3403, USA.
Lu
You
Y
Sun
Xun
X
Johnston
Julie
J
Calcedo
Roberto
R
Grant
Rebecca
R
Wilson
James M
JM
D000818:Animals; D018076:DNA, Complementary; D000229:Dependovirus / Q000235:genetics*; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D016679:Genome, Viral / Q000235:genetics*; D008099:Liver / Q000378:metabolism* / Q000821:virology*; D008252:Macaca fascicularis; D012703:Serotyping; D019076:Transgenes / Q000235:genetics*
D018076:DNA, Complementary