The preclinical data on an antisense oligonucleotide drug beingdeveloped by Isis Pharmaceuticals Inc. have been published inthe February issue of Antimicrobial Agents and Chemotherapy,the Carlsbad, Calif., company announced Wednesday.
The drug, ISIS 2105, is now in Phase II clinical trials fortreating genital warts. In particular, Isis scientists designed theantisense compound to attack human papilloma virus (HPV),which is the cause of most genital warts. The double-blindedtrial is designed to determine whether ISIS 2105 can delay orprevent wart recurrence following surgical removal. Currentlythere are no therapeutics that effective kill this virus andprevent its recurrence.
The development of specific anti-viral drugs against HPVhasAbeen hampered because the virus normally can't be grownin vitro or in vivo. To study the virus at all, it's been necessaryto "resort to molecular biology tricks," explained ChristopherMirabelli, Isis' executive vice president of research andpreclinical development. Scientists have been able to constructvectors containing segments of HPV DNA, transfect those intocultured cells, and examine the expression of the genetictranscript.
Isis scientists chose to examine a related bovine papillomavirus (BPV) as a model system for designing an anti-viralantisense construct. The bovine and human viruses are "quitesimilar in terms of the overall gene structure ... but at thenucleotide level these sequences are different enough that abovine-specific (antisense) compound doesn't work for thehuman strain," Mirabelli told BioWorld.
Isis scientists targeted the E2 gene product, which plays a rolein regulating viral transcription and DNA replication. Theytested antisense oligonucleotides against the E2 messenger RNAin the bovine virus, and then devised a similar model for HPV,from which they developed the antisense drug candidate ISIS2105.
-- Jennifer Van Brunt Senior Editor
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