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

Int J Cardiol. 2005 Apr 28;100(3):421-6. doi: 10.1016/j.ijcard.2004.09.003.

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 (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.

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.

MeSH terms

  • Animals
  • Dependovirus*
  • Gene Expression
  • Gene Transfer Techniques
  • Genetic Vectors
  • Lac Operon / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Transgenes / physiology*
  • Ventricular Function, Left