Human cytomegalovirus mutant with sequence-dependent resistance to the phosphorothioate oligonucleotide fomivirsen (ISIS 2922).
نویسندگان
چکیده
A human cytomegalovirus mutant that was isolated for resistance (10-fold) to the antisense oligonucleotide fomivirsen (ISIS 2922) exhibited cross-resistance to a modified derivative of fomivirsen with an identical base sequence but little or no resistance to an oligonucleotide with an unrelated sequence. No changes in the mutant's DNA corresponding to the fomivirsen target sequence were found.
منابع مشابه
Pharmacokinetics of a potential human cytomegalovirus therapeutic, a phosphorothioate oligonucleotide, after intravitreal injection in the rabbit.
The disposition of ISIS 2922, a phosphorothioate oligonucleotide for treatment of cytomegalovirus associated retinitis, was evaluated in rabbits. Vitreous humor and retina samples were collected from rabbits that received a single intravitreal injection of 66 microg [14C]-labeled ISIS 2922 and were analyzed using anion exchange HPLC. Four hr postdosing, the concentration of ISIS 2922 in vitreou...
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Retinal toxicity of ISIS 2922 and ISIS 4015, phosphorothioate oligonucleotides complementary to human cytomegalovirus (CMV) and herpes simplex virus (HSV) RNA, were evaluated. The intravitreal concentration of ISIS 2922 found not to cause permanent toxic changes in the rabbit retina was 10 microM and in the pig retina, 5 microM. The 3 microM concentration was associated with a transient inflamm...
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The kinetics of an intravitreally administered phosphorothioate oligonucleotide, ISIS 2922, were studied in cynomolgus monkeys. Vitreal and retinal concentrations were measured after administration of 11, 57, or 115 microg/eye. ISIS 2922 concentrations in vitreous and retina were compared, after single, weekly, or biweekly doses, for potential accumulation. ISIS 2922 levels were quantified usin...
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متن کاملVirucidal activity of a GT-rich oligonucleotide against herpes simplex virus mediated by glycoprotein B.
We have investigated the antiviral mechanism of a phosphorothioate oligonucleotide, ISIS 5652, which has activity against herpes simplex virus (HSV) in the low micromolar range in plaque reduction assays. We isolated a mutant that is resistant to this compound. Marker rescue and sequencing experiments showed that resistance was due to at least one of three mutations in the UL27 gene which resul...
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ورودعنوان ژورنال:
- Antimicrobial agents and chemotherapy
دوره 42 4 شماره
صفحات -
تاریخ انتشار 1998