Adeno-associated virus (AAV) has shown promise as a vector for cardiac gene transfer given its ability to stably integrate into the host genome and its lack of immune reactivity. This study examined the feasibility of AAV-mediated myocardial gene transfer in mice, the animal which, because of transgenic technology, has become the disease model of choice for cardiovascular research.AAV encoding the cytomegalovirus promoter driven LacZ reporter gene (10(7) LacZ-forming units per animal) or vehicle control was injected into the hearts of young adult C57Bl/6 mice by a transdiaphragmatic approach. At one, two, three, six, and twelve months post-injection, cardiac function was assessed by transthoracic echocardiography and hearts were assayed by X-gal histochemical staining.Echocardiography revealed normal left ventricular function in both AAV and control groups at all time points. X-gal staining of cryostat sections of hearts revealed uniform LacZ expression at all time points. There were minimal signs of immunologic infiltration by hematoxylin and eosin staining.AAV-mediated myocardial gene transfer by transdiaphragmatic injection can be conducted safely and results in long-term expression of the LacZ gene for at least one year without causing significant inflammatory response or adversely affecting LV systolic function.
View details for DOI 10.1016/j.ijcard.2004.09.003
View details for Web of Science ID 000228814600012
View details for PubMedID 15837086