Isis Pharmaceuticals Inc. scientists have constructed a seriesof oligonucleotides that inhibit in vitro a key genetic sequencein the viral expression of HIV.

Isis stock (NASDAQ:ISIP) jumped $2.75 on the news Friday,closing at $12.75.

Company scientists reported last week in the journal NucleicAcids Research on a series of phosphodiester andphosphorothioate antisense oligonucleotides that bind to amessenger RNA segment of HIV, the AIDS virus. The segment,known as TAR (trans-activating responsive sequence),stimulates viral gene expression and, ultimately, viralreplication.

Antisense drugs are designed to bind with messenger RNAmolecules to block the manufacture of disease-causingproteins.

The oligonucleotides disrupted the TAR structure and hence itsfunction. TAR binds an HIV regulatory protein known as tat(trans-activator), whose role is to stimulate transcription.Disruption of the TAR/tat interaction inhibits the normal HIVlife cycle.

"The importance of this paper is that it lays the foundation formolecules we haven't disclosed yet," said Isis Chief ExecutiveOfficer Stanley Crooke, referring to the oligonucleotides. "Themolecules we're now working on are 1,000- to 10,000-foldmore potent than the ones (reported) in this article."

Crooke emphasized the early stage of the reported research."Obviously, we have a long way to travel before we know ifthis will work in AIDS," he said.

-- Karen Bernstein BioWorld Staff

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