One year transgene expression with adeno-associated virus cardiac gene transfer

Y. Joseph Woo, Janet C.L. Zhang, Matthew D. Taylor, Jeffrey E. Cohen, Vivian M. Hsu, H. Lee Sweeney

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Background: 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. Methods: AAV encoding the cytomegalovirus promoter driven LacZ reporter gene (107 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)421-426
Number of pages6
JournalInternational Journal of Cardiology
Volume100
Issue number3
DOIs
StatePublished - Apr 28 2005

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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