Recombinant growth factor gene expression in vascular cells in vivo

E. G. Nabel, G. E. Plautz, G. J. Nabel

Research output: Contribution to journalArticle

Abstract

Several issues are important to the use of direct gene transfer as an investigative tool and as a potential therapeutic modality. Transfection efficiencies of different vectors must be improved and optimized. Retroviral vectors and DNA liposome conjugates currently used in animal models are low-efficiency vectors. Adenoviruses and adenoviral conjugates appear promising, but issues related to gene persistence, germ-line transmission, and stability of expression must be explored. Second, the pharmacology or dose-response properties of recombinant gene expression have not been investigated. It is not currently known how many cells must be transfected in an arterial segment in order to produce a desired biological effect. Our studies suggest that only a small population of cells is required to secrete a recombinant gene product into the local milieu. This gene product may then have local paracrine effects with amplification of the biological response, suggesting a 'gain of function.' Third, methods must be developed to target recombinant genes specifically to endothelial cells or smooth muscle cells using cell-specific promoters. Finally, gene expression should be regulated through inducible or repressible promoters. Nonetheless, during the past ten years a dramatic expansion in the fields of gene transfer and gene therapy has occurred. We have entered a new era in which molecular genetic techniques are being increasingly used to investigate the pathophysiology of cardiovascular disorders and to design potential therapies for these diseases. Although technical hurdles related to optimization of vectors and regulated gene expression must be solved, molecular genetic approaches will be increasingly used to study and treat cardiovascular diseases.

Original languageEnglish (US)
Pages (from-to)247-252
Number of pages6
JournalAnnals of the New York Academy of Sciences
Volume714
DOIs
StatePublished - 1994
Externally publishedYes

Fingerprint

Gene expression
Blood Vessels
Intercellular Signaling Peptides and Proteins
Genes
Gene transfer
Gene Expression
Cells
Gene therapy
Molecular Biology
Endothelial cells
Liposomes
Amplification
Muscle
Genetic Techniques
Electric lines
Animals
Adenoviridae
Germ Cells
Genetic Therapy
Smooth Muscle Myocytes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Recombinant growth factor gene expression in vascular cells in vivo. / Nabel, E. G.; Plautz, G. E.; Nabel, G. J.

In: Annals of the New York Academy of Sciences, Vol. 714, 1994, p. 247-252.

Research output: Contribution to journalArticle

Nabel, E. G. ; Plautz, G. E. ; Nabel, G. J. / Recombinant growth factor gene expression in vascular cells in vivo. In: Annals of the New York Academy of Sciences. 1994 ; Vol. 714. pp. 247-252.
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