title: Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection.
abstract: This study examines transgene expression and biodistribution of adeno-associated virus (AAV) pseudotyped 1-9 after tail vein (TV) injection in male mice. Using a cytomegalovirus (CMV)-luciferase transgene, the time-course of expression in each animal was tracked throughout the experiment. The animals were imaged at 7, 14, 29, 56, and 100 days after the TV injection. The total number of photons emitted from each animal was recorded, allowing examination of expression level and kinetics for each pseudotyped virus. The bioluminescence imaging revealed three expression levels (i) low-expression group, AAV2, 3, 4, and 5; (ii) moderate-expression group, AAV1, 6, and 8; and (iii) high-expression group, AAV7 and 9. In addition, imaging revealed two classes of kinetics (i) rapid-onset, for AAV1, 6, 7, 8, and 9; and (ii) slow-onset, for AAV2, 3, 4, and 5. We next evaluated protein expression and viral genome copy numbers in dissected tissues. AAV9 had the best viral genome distribution and highest protein levels. The AAV7 protein and genome copy numbers were comparable to those of AAV9 in the liver. Most surprisingly, AAV4 showed the greatest number of genome copies in lung and kidney, and a high copy number in the heart. AAV6 expression was observed in the heart, liver, and skeletal muscle, and the genome distribution corroborated these observations.
authors.affiliation: Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Carmela
authors.initials: C
authors.lastname: Zincarelli
authors.forename: Stephen
authors.initials: S
authors.lastname: Soltys
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rengo
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Rabinowitz
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics* / Q000378:metabolism*; D004452:Echocardiography / Q000379:methods; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D016678:Genome; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D008957:Models, Genetic; D013997:Time Factors; D019076:Transgenes