title: Adeno-associated virus (AAV) serotype 9 provides global cardiac gene transfer superior to AAV1, AAV6, AAV7, and AAV8 in the mouse and rat.
abstract: Heart disease is the leading cause of morbidity and mortality. Cardiac gene transfer may serve as a novel therapeutic approach. This investigation was undertaken to compare cardiac tropisms of adeno-associated virus (AAV) serotypes 1, 6, 7, 8, and 9. Neonatal mice were injected with 2.5 x 10(11) genome copies (GC) of AAV serotype 1, 6, 7, 8, or 9 expressing LacZ under the control of the constitutive chicken beta-actin promoter with cytomegalovirus enhancer promoter via intrapericardial injection and monitored for up to 1 year. Adult rats were injected with 5 x 10(11) GC of the AAV vectors via direct cardiac injection and monitored for 1 month. Cardiac distribution of LacZ expression was assessed by X-Gal histochemistry, and beta-galactosidase activity was quantified in a chemiluminescence assay. Cardiac functional data and biodistribution data were also collected in the rat. AAV9 provided global cardiac gene transfer stable for up to 1 year that was superior to other serotypes. LacZ expression was relatively cardiac specific, and cardiac function was unaffected by gene transfer. AAV9 provides high-level, stable expression in the mouse and rat heart and may provide a simple alternative to the creation of cardiac-specific transgenic mice. AAV9 should be used in rodent cardiac studies and may be the vector of choice for clinical trials of cardiac gene transfer.
authors.affiliation: Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. bish@mail.med.upenn.edu
authors.forename: Lawrence T
authors.initials: LT
authors.lastname: Bish
authors.forename: Kevin
authors.initials: K
authors.lastname: Morine
authors.forename: Meg M
authors.initials: MM
authors.lastname: Sleeper
authors.forename: Julio
authors.initials: J
authors.lastname: Sanmiguel
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Guangping
authors.initials: G
authors.lastname: Gao
authors.forename: James M
authors.initials: JM
authors.lastname: Wilson
authors.forename: H Lee
authors.initials: HL
authors.lastname: Sweeney
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000229:Dependovirus / Q000145:classification / Q000235:genetics*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D013045:Species Specificity; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D001616:beta-Galactosidase
references.citation: J Virol. 2005 Jun;79(11):6801-7
references.pmid: 15890919
references.citation: Mol Ther. 2004 Sep;10(3):604-8
references.pmid: 15336660
references.citation: Gene Ther. 2007 Nov;14(22):1605-9
references.pmid: 17898796
references.citation: Circ Res. 2006 Aug 18;99(4):e3-9
references.pmid: 16873720
references.citation: Gene Ther. 2003 Dec;10(26):2112-8
references.pmid: 14625565
references.citation: J Gene Med. 2008 Feb;10(2):132-42
references.pmid: 18064719
references.citation: Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11854-9
references.pmid: 12192090
references.citation: J Mol Cell Cardiol. 1999 Apr;31(4):721-32
references.pmid: 10329200
references.citation: Cardiovasc Res. 2006 Apr 1;70(1):6-8
references.pmid: 16524565
references.citation: Mol Ther. 2006 Jul;14(1):45-53
references.pmid: 16713360
references.citation: J Virol. 2004 Jun;78(12):6381-8
references.pmid: 15163731
references.citation: Gene Ther. 2007 Jul;14(13):989-97
references.pmid: 17251988
references.citation: Mol Ther. 2004 Dec;10(6):981-9
references.pmid: 15564130
references.citation: Circulation. 2007 May 15;115(19):2506-15
references.pmid: 17470693
references.citation: Cardiovasc Res. 2006 Apr 1;70(1):70-8
references.pmid: 16448634
references.citation: J Card Fail. 2008 Jun;14(5):355-67
references.pmid: 18514926
references.citation: Cardiovasc Res. 2007 Feb 1;73(3):453-62
references.pmid: 17097076
references.citation: Mol Ther. 2008 Jun;16(6):1073-80
references.pmid: 18414476
references.citation: Int J Cardiol. 2005 Apr 28;100(3):421-6
references.pmid: 15837086
references.citation: Gene Ther. 2001 Aug;8(16):1248-54
references.pmid: 11509958
references.citation: J Virol. 2001 Jul;75(13):6199-203
references.pmid: 11390622
references.citation: Circulation. 2003 Sep 30;108(13):1626-32
references.pmid: 12952841
references.citation: J Mol Cell Cardiol. 2007 Apr;42(4):852-61
references.pmid: 17300800
references.citation: Blood. 2005 May 1;105(9):3458-64
references.pmid: 15479726
references.citation: Genet Vaccines Ther. 2007 Dec 10;5:13
references.pmid: 18070352
references.citation: Basic Res Cardiol. 2001 May-Jun;96(3):227-36
references.pmid: 11403416
references.citation: J Heart Lung Transplant. 2008 May;27(5):554-60
references.pmid: 18442723
references.citation: Transpl Int. 2007 Jun;20(6):550-7
references.pmid: 17403107
references.citation: Gene Ther. 2007 Sep;14(18):1319-29
references.pmid: 17611587
references.citation: J Thromb Haemost. 2007 Jan;5(1):16-24
references.pmid: 17002653
references.citation: Mol Ther. 2005 Jun;11(6):980-5
references.pmid: 15922969