Gene transfer and models of gene therapy for the myocardium

M. Yvonne Alexander, Keith A Webster, Patricia H. McDonald, Howard M. Prentice

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

1. Gene transfer into the myocardium can be achieved through direct injection of plasmid DNA or through the delivery of viral vectors, either directly or through the coronary vasculature. Direct DNA injection has proven extremely valuable in studies aimed at characterizing the activities of promoter elements in cardiac tissue and for examining the influence of the pathophysiological state of the myocardium on expression of transferred foreign genes. 2. Viral vectors, in particular adenoviruses and adeno- associated virus, are capable of transfecting genetic material with high transduction efficiencies and have been applied to a range of model systems for in vivo gene transfer. Efficient gene transfer has been achieved into the coronary vessels and surrounding myocardium by intracoronary infusion of adenovirus. 3. Because the immunogenicity of viral vectors can limit transgene expression, much attention has been paid to strategies for circumventing this, including the development of new modified adenovirus and adeno-associated virus vectors that do not elicit significant inflammatory responses. While cellular transplantation may prove valuable for the repair of myocardial tissue, confirmation of its value awaits establishment of a functional improvement in the myocardium following cell grafting. 4. Because gene transfer into the myocardium can now be achieved with high efficiency in the absence of significant inflammatory responses, the ability to regulate foreign gene expression in response to an endogenous disease phenotype will enable the development of new effective viral vectors with direct clinical applicability for specified therapeutic targets.

Original languageEnglish
Pages (from-to)661-668
Number of pages8
JournalClinical and Experimental Pharmacology and Physiology
Volume26
Issue number9
DOIs
StatePublished - Sep 28 1999

Fingerprint

Genetic Therapy
Myocardium
Adenoviridae
Genes
Dependovirus
Injections
DNA
Transgenes
Coronary Vessels
Plasmids
Transplantation
Phenotype
Gene Expression

Keywords

  • Adenovirus
  • Animal models of foreign gene delivery
  • Gene therapy
  • Gene transfer
  • Ischaemia
  • Myocardial
  • Myocardium
  • Viral vectors

ASJC Scopus subject areas

  • Physiology
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Gene transfer and models of gene therapy for the myocardium. / Yvonne Alexander, M.; Webster, Keith A; McDonald, Patricia H.; Prentice, Howard M.

In: Clinical and Experimental Pharmacology and Physiology, Vol. 26, No. 9, 28.09.1999, p. 661-668.

Research output: Contribution to journalArticle

Yvonne Alexander, M. ; Webster, Keith A ; McDonald, Patricia H. ; Prentice, Howard M. / Gene transfer and models of gene therapy for the myocardium. In: Clinical and Experimental Pharmacology and Physiology. 1999 ; Vol. 26, No. 9. pp. 661-668.
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