Systematic evaluation of AAV vectors for liver directed gene transfer in murine models.
Vectors based on adeno-associated viruses (AAVs) are being evaluated for use in liver-directed gene therapy. Candidates have been preselected on the basis of capsid structure that plays an important role in determining performance profiles. We describe a comprehensive and statistically powered set of mouse studies designed to compare the performance of vectors based on seven novel AAV capsids. The key criteria used to select candidates for successful gene therapy are high level and stable transgene expression in the absence of toxicity. Based on these criteria, the best performing vectors, AAV8, AAVhu.37, and AAVrh.8, will be further evaluated in nonhuman primates (NHPs).
Wang
Lili
L
Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Wang
Huan
H
Bell
Peter
P
McCarter
Robert J
RJ
He
Jianping
J
Calcedo
Roberto
R
Vandenberghe
Luk H
LH
Morizono
Hiroki
H
Batshaw
Mark L
ML
Wilson
James M
JM
D000818:Animals; D000229:Dependovirus / Q000145:classification / Q000235:genetics*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics*; D007275:Injections, Intravenous; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010802:Phylogeny; D014161:Transduction, Genetic / Q000379:methods*