By Wafik S. El-Deiry
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Ellison, K. , et al. (1993) Single intraluminal delivery of antisense cdc2 kinase and proliferating-cell nuclear antigen oligonucleotides results in chronic inhibition of neointimal hyperplasia. Proc. Natl. Acad. Sci. USA 90, 8474–8478. , et al. (1994) Transcatheter delivery of c-myc antisense oligomers reduces neointimal formation in a porcine model of coronary artery balloon injury. Circulation 90, 944–951. Cornish, K. , Iversen, P. , and Bayever, E. (1993) Cardiovascular effects of a phosphorothioate oligonucleotide with sequence antisense to p53 in the conscious rhesus monkey.
And Andino, R. (2002) Short interfering RNA confers intracellular antiviral immunity in human cells. Nature 418, 430–434. 83. , and Taira, K. (2003) Comparison of the suppressive effects of antisense oligonucleotides and siRNAs directed against the same targets in mammalian cells. Antisense Nucleic Acid Drug Dev. 13, 1–7. Antisense Inhibition 33 84. 84 Bertrand, J. , et al. (2002) Comparison of antisense oligonucleotides and siRNAs in cell culture and in vivo. Biochem. Biophys. Res. Commun. 29, 1000–1004.
Equation 1 can be simplified to Eq. 2 as follows: [MYC]t = [MYC]ss + injury-induced MYC synthesis - MYCturnover (2) Critical questions in the development of a delivery tool for AVI-4126 are as follows: (1) What is the time course for MYC synthesis? (2) Can AVI-4126 inhibit MYC expression in the appropriate cells in the vessel wall following appropriate magnitude and duration of injury? (3) Are the amount and duration of AVI-4126 delivered relative to injury to the vessel wall sufficient? The expected result of a study in which the initial synthesis of MYC is not inhibited is shown in Fig.