Adeno-associated virus (AAV) serotype 9 provides global cardiac gene transfer superior to AAV1, AAV6, AAV7, and AAV8 in the mouse and rat

LT Bish, K Morine, MM Sleeper, J Sanmiguel… - Human gene …, 2008 - liebertpub.com
LT Bish, K Morine, MM Sleeper, J Sanmiguel, D Wu, G Gao, JM Wilson, HL Sweeney
Human gene therapy, 2008liebertpub.com
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× 1011 genome copies (GC) of AAV serotype 1, 6, 7, 8, or 9
expressing LacZ under the control of the constitutive chicken β-actin promoter with
cytomegalovirus enhancer promoter via intrapericardial injection and monitored for up to 1 …
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 × 1011 genome copies (GC) of AAV serotype 1, 6, 7, 8, or 9 expressing LacZ under the control of the constitutive chicken β-actin promoter with cytomegalovirus enhancer promoter via intrapericardial injection and monitored for up to 1 year. Adult rats were injected with 5 × 1011 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 β-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.
Mary Ann Liebert