title: AAV-8 is more efficient than AAV-9 in transducing neonatal dog heart.
abstract: Adeno-associated virus serotype-8 and 9 (AAV-8 and 9) are the leading candidate vectors to test bodywide neonatal muscle gene therapy in large mammals. We have previously shown that systemic injection of 2-2.5×10(14) viral genome (vg) particles/kg of AAV-9 resulted in widespread skeletal muscle gene transfer in newborn dogs. However, nominal transduction was observed in the heart. In contrast, robust expression was achieved in both skeletal muscle and heart in neonatal dogs with 7.14-9.06×10(14) vg particles/kg of AAV-8. To determine whether superior cardiac transduction of AAV-8 is because of the higher vector dose, we delivered 6.14×10(14) and 9.65×10(14) vg particles/kg of AAV-9 to newborn puppies via the jugular vein. Transduction was examined 2.5 months later. Consistent with our previous reports, we observed robust bodywide transduction in skeletal muscle. However, increased AAV dose only moderately improved heart transduction. It never reached the level achieved by AAV-8. Our results suggest that differential cardiac transduction by AAV-8 and AAV-9 is likely because of the intrinsic property of the viral capsid rather than the vector dose.
authors.affiliation: 1 Department of Molecular Microbiology and Immunology, School of Medicine, The University of Missouri , Columbia, MO 65212.
authors.forename: Xiufang
authors.initials: X
authors.lastname: Pan
authors.forename: Yongping
authors.initials: Y
authors.lastname: Yue
authors.forename: Keqing
authors.initials: K
authors.lastname: Zhang
authors.forename: Chady H
authors.initials: CH
authors.lastname: Hakim
authors.forename: Kasun
authors.initials: K
authors.lastname: Kodippili
authors.forename: Thomas
authors.initials: T
authors.lastname: McDonald
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Duan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D000229:Dependovirus / Q000145:classification* / Q000235:genetics*; D004285:Dogs; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007275:Injections, Intravenous; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic; D014161:Transduction, Genetic