Down-regulation of c-MYC antigen expression in lymphocytes of Emu-c-myc transgenic mice treated with anti-c-myc DNA methylphosphonates.
In transgenic mice bearing a murine immunoglobulin enhancer/c-myc fusion transgene (Emu-myc), it was found that antisense DNA methylphosphonates targeted against c-myc mRNA inhibited production of c-MYC protein in peripheral lymphocytes. The decrease in protein was measured 3-4 h after i.v. administration of a 300-nmol dose. c-MYC was detected by immunofluorescence of fixed cells stained with an anti-c-MYC antiserum. In addition, DNA methylphosphonates did not induce acute toxicity following i.v. administration of a 300-nmol dose. An identically administered scrambled sequence oligomer did not decrease c-MYC protein or induce toxicity. Finally, recovery of DNA methylphosphonates from the blood plasma of treated mice indicated that the oligomers remained intact up to 3 h, while their concentrations decreased rapidly for the first h, then slowly decreased over the next 2 h. This is the first demonstration of sequence-specific antisense DNA methylphosphonate inhibition of gene expression in the bloodstream of an animal model.[1]References
- Down-regulation of c-MYC antigen expression in lymphocytes of Emu-c-myc transgenic mice treated with anti-c-myc DNA methylphosphonates. Wickstrom, E., Bacon, T.A., Wickstrom, E.L. Cancer Res. (1992) [Pubmed]
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