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Review
. 2000 Nov;106(9):1071-5.
doi: 10.1172/JCI11459.

Therapeutic applications of transcription factor decoy oligonucleotides

M J Mann  1 , V J Dzau
Affiliations
Review

Therapeutic applications of transcription factor decoy oligonucleotides

M J Mann et al. J Clin Invest. 2000 Nov.
No abstract available

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Figures

Figure 1
Figure 1
The decoy oligonucleotide approach to block the function of the transcription factor E2F. In quiescent cells (a), the factor is sequestered in a protein complex. During cell cycle progression (b), the complex is phosphorylated and free E2F is released. The factor binds to its consensus binding sequence in the promoter regions of multiple cell cycle regulatory genes. The introduction into the nucleus of decoy oligonucleotides that bear the consensus binding sequence (c) prevents interaction of the factor with its promoter targets, thus inhibiting the upregulation of cell cycle genes and blocking proliferation.
Figure 2
Figure 2
Vein grafts are initially thin-walled vessels that must undergo wall thickening to resist increased stress in the arterial circulation. The neointimal hyperplasia that produces this thickening, however, involves the proliferation of activated smooth muscle cells that create a substrate for accelerated atherosclerosis and subsequent graft occlusion. Blocking neointimal hyperplasia, as we have done using an E2F decoy oligonucleotide, induces an adaptive hypertrophic thickening of the medial layer of the vessel, yielding hemodynamic stability without increased susceptibility to atherosclerotic disease.
Figure 3
Figure 3
Primary vein graft patency with or without intraoperative treatment of the grafts with E2F decoy oligonucleotides. In a small cohort of patients at high risk for primary graft failure, primary patency at 12 months was improved with E2F decoy blockade of cell cycle gene expression and neointimal hyperplasia (P = 0.04). The absence of ongoing failures beyond the first 6 months in the treated group may suggest a long-term stabilization of graft wall architecture via this one-time, intraoperative gene manipulation approach. (From ref. 11).
See this image and copyright information in PMC

References

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