Antiviral activity and ocular kinetics of antisense oligonucleotides designed to inhibit CMV replication

  • Henry S
  • Miner R
  • Drew W
 et al. 
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PURPOSE: To compare the antiviral activity and ocular distribution of first- and second-generation antisense oligonucleotides intended for the treatment of cytomegalovirus (CMV) retinitis. METHODS: The antiviral activity of ISIS 13312 and ISIS 2922 (Isis Pharmaceuticals, Inc., Carlsbad, CA) against 10 clinical CMV isolates was compared with a plaque-reduction assay. The ocular pharmacokinetics were compared after intravitreal injection in rabbits (36-90 microg) and monkeys (125-500 microg). Vitreous and/or retina were collected after single and multiple injections to characterize ocular distribution, clearance, and accumulation. Oligonucleotide concentrations were measured by capillary gel electrophoresis and immunohistochemical techniques. RESULTS: ISIS 13312 and ISIS 2922 demonstrated comparable antiviral activity that was consistent among the 10 clinical isolates examined (50% inhibitory concentration [IC(50)],

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  • SCOPUS: 2-s2.0-0034788245
  • ISSN: 01460404
  • PMID: 11581212
  • SGR: 0034788245
  • PUI: 32954876
  • ISBN: 0146-0404


  • S. P. Henry

  • R. C. Miner

  • W. L. Drew

  • J. Fitchett

  • C. York-Defalco

  • L. M. Rapp

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