title: Selective tropism of the recombinant adeno-associated virus 9 serotype for rat cardiac tissue.
abstract: BACKGROUND
  Cardiac gene transfer may serve as a novel therapeutic approach for heart disease. Numerous serotypes of recombinant adeno-associated virus (rAAV) have been identified with variable tropisms to cardiac tissue.
  
  
  METHODS
  Both in vitro and in vivo experiments were undertaken to compare cardiac tropisms of rAAV-2, 5, 7, 8 and 9. For the in vitro studies, 10(7) vector genome (vg) of rAAV-2, 5, 7, 8 or 9 were used to transduce both rat neonatal cardiac myocytes (RNCM) and fibroblasts (RNCF). For the in vivo studies, 4 x 10(10) vg of rAAV-2, 5, 7, 8 or 9, and 4 x 10(11) vg of rAAV8 or 9 were administered in 5-day-old rats via a relatively non-invasive intracardiac injection. One and two months post-administration, green fluorescent protein (GFP) expression in tissues was visualized and GFP mRNA was quantified by the real-time polymerase chain reaction.
  
  
  RESULTS
  At 3 days post-viral transduction, rAAV9 and rAAV2 produced the highest transducing efficiency in RNCM. Only rAAV2 elicited any transduction in the RNCF. The results obtained in vivo indicated that the order for transduction efficiency in the heart was: rAAV9 > rAAV8 > rAAV7 > rAAV2 = rAAV5. The transduction efficiency order in the liver was: rAAV2 > rAAV5 > rAAV7 > rAAV8 > rAAV9. Injection of a higher dose (4 x 10(11) vg) of rAAV9 provided more widespread and highly cardiac-selective GFP expression in the heart than rAAV8. Zero to minimal expression of GFP was found in the lung and kidney for both doses of all rAAV serotypes utilized.
  
  
  CONCLUSIONS
  Collectively, the results obtained in the present study suggest that rAAV9 provides the most selective and stable transduction efficiency in cardiac tissue, and this expression was primarily exhibited in cardiac myocytes.
authors.affiliation: Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL 32610-0487, USA. yanfeiqi@ufl.edu
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Qi
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
authors.forename: Vinayak
authors.initials: V
authors.lastname: Shenoy
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Li
authors.forename: William W
authors.initials: WW
authors.lastname: Hauswirth
authors.forename: Colin
authors.initials: C
authors.lastname: Sumners
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Katovich
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000229:Dependovirus / Q000145:classification / Q000235:genetics* / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000821:virology; D009928:Organ Specificity / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012703:Serotyping; D014018:Tissue Distribution; D014161:Transduction, Genetic; D019076:Transgenes / Q000235:genetics; D056189:Viral Tropism
chemical_list: D012333:RNA, Messenger; D049452:Green Fluorescent Proteins