Effect of dose and plasma concentration on liver uptake and pharmacologic activity of a 2'-methoxyethyl modified chimeric antisense oligonucleotide targeting PTEN.

@article{Geary2009EffectOD,
  title={Effect of dose and plasma concentration on liver uptake and pharmacologic activity of a 2'-methoxyethyl modified chimeric antisense oligonucleotide targeting PTEN.},
  author={Richard S. Geary and Ed Wancewicz and John Matson and Megan E. Pearce and Andrew M. Siwkowski and Eric E Swayze and Frank Bennett},
  journal={Biochemical pharmacology},
  year={2009},
  volume={78 3},
  pages={
          284-91
        }
}
The role of dose and plasma concentration on liver tissue uptake and resulting antisense pharmacology using a chemically modified antisense oligonucleotide (ASO) targeting PTEN was assessed in mice. A single bolus s.c. dose of 60 mg/kg in mice showed a time-dependent reduction in liver PTEN mRNA that was maximal at 48-72 h and returned to near control levels by 20 days after administration. These pharmacodynamics are in good agreement with liver concentrations of ASO and are consistent with… CONTINUE READING

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